Name: 1486-51-7|4-(Benzyloxy)benzoic acid|98%
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[ 1486-51-7 ]
[ 1486-50-6 ]

Yield	Reaction Conditions	Operation in experiment
100%	With oxalyl dichloride; N,N-dimethyl-formamide at 20℃; for 2h;	4 Preparation of 4-benzyloxybenzoyl chloride. Oxalyl chloride (6.5 ml, 75.6 mmol, 1.5 eq.) was added to a suspension of 4-benzyloxybenzoic acid (11.5 g, 50.4 mmol) followed by the addition of DIVIF (0.3 mL, cat.). Gas formation was observed and the mixture was stirred for 2 hours at room temperature during which it became homogeneous. The volatile compounds were removed under reduced pressure (45 °C) and the residue was stripped with toluene, affording a light pink solid (13.4 g, quant.).
99%	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 23℃; for 2h;
98%	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane for 2h;

98%	With thionyl chloride for 5h; Heating;
98%	With oxalyl dichloride In dichloromethane for 3h; Heating / reflux;	32 Example 32: Synthesis [OF 5- (4-BENZYLOXY-PHENYL)-6-CYCLOHEXYL-7-OXO-4,] 7-dihydro- pyrazolo [1, 5-a] pyrimidine-2-carboxylic acid To [A] mixture [OF 5.] 0 g (21. [9] [MMOL) OF 4-BENZYLOXY-BENZOIC] acid [I71 25 ML OF] dichloromethane (DCM) was [ADDED DROPWISE 10 ML (114 MMOL) OF OXALYL] chloride, followed [BY S, UL OF DIMETHYLFORMAMIDE] (DMF cat) and the reaction mixture was heated at reflux for 3 h, and concentrated to [GIVE 5. 32 G (98/) OF DESIRED 4-BENZYLOXY-BENZOYL] chloride as a yellow solid as indicated by 1H NMR. The product was used without any further purification in the next step. A solution of 0.35 mL (2.5 mmol) [OF DIISOPROPYLAMINE (IPR2NH) IN] 7 mL of tetrahydrofuran (THF) was flushed with argon and cooled [TO-78 C.] To this solution was added dropwise 1 mL (2.5 mmol) [OF N-BUTYLLIT7AIUM (RZBULI)] 2. 5 [M SOLUTION IN HEXANE,] and the resulting mixture was stirred at-78 C for 20 min, after which time 0.33 mL (2 mmol) of [METLAYL CYCLOHEXYLACETATE] was added dropwise. The mixture was allowed to warm up to rt for 40 min, then it was cooled again [TO-78 C,] and a solution of 0.592 g (2.4 mmol) [OF 4-] [BEF2ZYLOXY-BENZOYL CHLORIDE] in 8 mL of THF was added dropwise, and the resulting mixture was allowed to warm up to rt, and stirred at rt overnight under argon. The reaction mixture was quenched on ice by the addition of saturated ammonium chloride solution, and extracted with ethyl acetate. The combined organic extracts were washed with water, brine, dried over sodium sulfate and concentrated to give 0.83 g of a yellow solid residue which was chromatographed on silica gel (Biotage; 25% hexane in dichloromethane) to afford 0.306 g (42% yield) of desired [3- (4-BENZYLOXY-PHENYL)-2-CYCLOHEXYL-3-OXO-PROPIONIC ACID NAETHYL ESTER] as a white solid as indicated by 1H NMR; [LC-MS-CALCD] for [C23H2604] [[M++HL +] : 367. 18, found: [367.] 2. A mixture of 274 mg (0.747 mmol) of [3-(4-BENZYLOXY-PHE7LYL)-2-CYCLOHEXYL-3-OXO-] propionic acid methyl ester, 106 mg (0.747 mmol) of 5-amino-1H-pyrazole-3-carboxylic acid methyl ester, 15 mg (10 mol%) of p-to9luenesulfonic acid monohydrate (PTSA), and 10 mL of toluene was heated at reflux for 88 h. The reaction mixture was then concentrated to a residue which was chromatographed on silica gel (Biotage; gradient elution 2% to 20% ethyl acetate in dichloromethane) to afford 55 mg (16% yield) of desired 5-(4-benzyloxy-phenyl)-6-cyclohexyl- [7-OXO-4,] 7-dihydro-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid methyl ester as a solid as indicated [BY 1H] NMR; LC-MS-calcd for [C27H27] [N304 [M++H] + :] 458.2, found: 458.2. This material was then converted to [5- (4-BENZYLOXY-PHENYL)-6-CYCLOHEXYL-7-OXO-4,] 7- dihydro-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid via the well known LiOH saponification protocol (55% yield, entry 538); LC-MS-calcd for [C26H25N304] [[M++H] +] : 444.18, found: 444.2.
77%	With thionyl chloride
	With phosphorus(V) chloride; benzene
	With thionyl chloride
	With thionyl chloride for 1h; Heating;
	With thionyl chloride In dichloromethane for 1.5h; Heating;
	With thionyl chloride In N,N-dimethyl-formamide at 60℃; for 0.5h;
	With oxalyl dichloride; triethylamine In dichloromethane at 25℃; for 0.416667h;
	With thionyl chloride
	With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 25℃; for 3h;
	With oxalyl dichloride; N,N-dimethyl-formamide In toluene at 40 - 45℃;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane
	With oxalyl dichloride; N,N-dimethyl-formamide In toluene
	With oxalyl dichloride In dichloromethane at 20℃; for 8h;
	With thionyl chloride; N,N-dimethyl-formamide Heating;
	With oxalyl dichloride; N,N-dimethyl-formamide In 1,2-dichloro-ethane at 20℃; for 2h;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 4h;
	With oxalyl dichloride; triethylamine In dichloromethane at 20℃; for 0.5h;
	With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 5h;
	With thionyl chloride In benzene	1 4-(Benzyloxy)benzoyl Chloride (10) 4-(Benzyloxy)benzoyl Chloride (10) A solution of 4-benzyloxybenzoic acid (2.50 g, 1.0 mmol) and thionyl chloride (1.2 mL, 16 mmol) in benzene (35 mL) was refluxed for 3 h under an argon atmosphere. The reaction mixture was cooled to rt and concentrated on a rotary evaporator. The residue was re-evaporated with benzene (2*) to afford the acid chloride as a white solid.
	With thionyl chloride In dichloromethane; N,N-dimethyl-formamide	9.b b) b) 4-benzyloxybenzoyl chloride To a mixture of 4-benzyloxybenzoic acid (2.28 g, 10 mmole) in 20 ml dried dichloromethane were added five drops of DMF and 2.5 ml thionyl chloride. The mixture was refluxed for three hours and evaporated under reduced pressure. Yield: 2.45 g=100%
	With thionyl chloride In dichloromethane; N,N-dimethyl-formamide	36.b (1S,2S)-N-[cis-2-(6-fluoro-2-O-3-propionylphenyl)-cyclopropyl]-N'-(5-cyanopyrid-2-yl) urea-O-4-hydroxybenzoate b) 4-benzyloxybenzoyl chloride. To a mixture of 4-benzyloxybenzoic acid (2.28 g, 10 mmole) in 20 ml dried dichloromethane were added five drops of DMF and 2.5 ml thionyl chloride. The mixture was refluxed for three hours and evaporated under reduced pressure. Yield: 2.45 g=100%
	With oxalyl dichloride In dichloromethane for 2h;	3 4-benzyloxybenzoic acid (1 g, 4.4 mmol) was added to anhydrous CH2Cl2 (11 mL). A catalytic amount of DMF (5 drops) was added along with oxalyl chloride in CH2Cl2 (2M, 5.75 mL) and the reaction stirred for 2 h. The solvents were evaporated and the crude 4-benzyloxybenzoyl chloride was used directly. SG00618 was prepared following the method for SG00612 using 4-benzylbenzoyl chloride. Yield 49 mg.
	With thionyl chloride In N,N-dimethyl-formamide	1.s First step First step Amounts of 11.4 g (50 mmole) of 4-benzyloxybenzoic acid, 36.6 ml (0.5 mole) of thionyl chloride, and 0.1 ml of DMF were mixed and stirred at 70° C for 2 hours, followed by heating under reflux for one hour. After the refluxing, unreacted thionyl chloride was obtained to give 4-benzyloxybenzoic acid chloride of the desired product.
	With thionyl chloride	1.ii (ii) (ii) Preparation of p-benzyloxybenzoic acid chloride Thionyl chloride (63.1 g, 0.53 mol) was added to p-benzyloxybenzoic acid (100.0 g, 0.44 mol), followed by refluxing the mixture for about 2 hours, and completely removing excess thionyl chloride by distillation under reduced pressure to obtain p-benzyloxybenzoic acid chloride (63.4 g).
	With thionyl chloride In Trichloroethylene	3.b (3b) (3b) 4-Benzyloxybenzoyl chloride A solution of 164.7 g 4-benzyloxybenzoic acid obtained in step (a) and 80 ml of thionyl chloride in 750 ml of trichloroethylene was refluxed with stirring for 3 hrs. The crystalline residue obtained after evaporation was recrystallized from petroleum ether b.p. 80°-110° C. The identity of the product was confirmed with NMR. Yield: 165.8 g (93%) NMR δppm: 5.2 2H (s); 7.6 9H (m) (CDCl3, TMS) STR54
	With thionyl chloride	2.i (i) (i) Preparation of optically active 4-(1-methylheptyloxycarbonyl)phenol Thionyl chloride (140 g, 1.18 mol) was added to 4-benzyloxybenzoic acid (220 g, 0.98 mol), followed by refluxing the mixture for about 2 hours, thereafter removing excess thionyl chloride under reduced pressure to obtain 4-benzyloxybenzoic chloride (210 g).
	With thionyl chloride Heating;
	With oxalyl dichloride In dichloromethane at 65℃; for 2h;
	With thionyl chloride for 4h; Heating / reflux;	i-4.A Step A: Preparation of ethyl 4-[4-("benzyloxy)benzoyl]benzoate (i-4a); 4-Benzyloxybenzoic acid (1.40 g, 5.70 mmol) was dissolved in thionyl chloride (4.0 mL), and the resulting reaction mixture was heated to reflux for 4h. The reaction mixture was cooled to rt and concentrated in vacuo to afford a crude solid that was added to a stirred solution of dichlorobis(triphenylphosphine) palladium(II) (0.40 g, 0.57 mmol) and 4-ethoxy- carbonylphenylzinc iodide (23 ml of a 0.5 M solution in THF) in THF (23 mL) at 0 0C. After 2 h, the reaction mixture was quenched with saturated aqueous ammonium chloride and extracted with EtOAc. The combined organics were dried (Na2SO4) and concentrated in vacuo.Purification of the crude residue by flash chromatography on silica gel (gradient elution; 15%- 35% EtOAc/hexanes as eluent) afforded the title compound i-4a. m/z (ES) 361 (MH)+.
	With oxalyl dichloride In dichloromethane at 20℃; for 20h;	17.17.1 17.1 Synthesis of 4-(benzyloxy)benzoyl chloride a57. A solution of 4-(benzyloxy)benzoic acid a45 (17.76 g, 77.8 mmol, 1 eq) in dichloromethane (700 ml) and λ/,λ/-dimethylformamide (400 μl) is treated with oxalyl chloride (9.2 ml, 85.58 mmol, 1.1 eq). The mixture is stirred for 20 h at 200C. The mixture is then concentrated under reduced pressure and used as such in the next step.
	With thionyl chloride In dichloromethane; N,N-dimethyl-formamide at 0℃; for 2h; Inert atmosphere;
	With thionyl chloride for 3h; Inert atmosphere;
	With thionyl chloride Reflux;
	With thionyl chloride; N,N-dimethyl-formamide In dichloromethane at 0℃; Reflux;
	With oxalyl dichloride; N,N-dimethyl-formamide In toluene
	With thionyl chloride at 78℃; for 4h;	23.3 Step 3: A solution of 4-(benzyloxy)benzoic acid (1.37 g, 6 mmol) and thionyl chloride (12 mL) was heated at 78 0C for 4 h. The reaction was concentrated under reduced pressure. Toluene was added and the resulting solution was dried in vacuo. The toluene evaporation procedure was repeated (2x). The crude 4-(benzyloxy)benzoyl chloride was dried under vacuum for 2 h and used without further purification in the next reaction.
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0℃; for 16h;	31.1 4-(Benzyloxy)benzoic acid (4.73 g, 20.72 mmol) was suspended in CH2Cl2 (50 mL). The suspension was cooled to 0 0C. To this suspension was added oxalyl chloride (3.63 mL, 41.4 mmol) followed by N, N-dimethylformamide (0.24 mL, 3.11 mmol) dropwise. The reaction was stirred for 16 hours. The reaction mixture was concentrated under reduced pressure, diluted with toluene, and concentrated under reduced pressure. The isolated solid was used directly for the next reaction without further purification.
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 3.5h; Inert atmosphere;
	With oxalyl dichloride In tetrahydrofuran; dichloromethane	6.a To a solution of 4-benzyloxybenzoic acid (1.0 g, 4.39 mmol) in THF (5 mL) was added oxalyl chloride (2.7 mL, 2.0 M in methylene chloride) followed by 1 drop of dimethylformamide. Vigorous evolution of gas was observed. After stirring for 1 hr, the mixture was concentrated in vacuo and was used immediately in the next reaction
	With thionyl chloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃;	22.A Preparation 22: 4-(1-Methyl-1 H-tetrazol-5-yl)phenolA) 4-(Benzyloxy)-N-methylbenzamideTo a flask charged with thionyl chloride (0.35 mL, 4.82 mmol) was added a solution of commercially available 4-benzyloxybenzoic acid (1.00 g, 4.38 mmol) in 10 mL of dichloromethane and 0.01 mL of Λ/,Λ/-dimethylformamide at zero degrees Celsius with stirring. The ice bath was removed and the solution was stirred for 4 hours at room temperature. The mixture was concentrated in vacuo to give a white solid. This solid was taken up in 10 mL of methyl amine (2 M in tetrahydrofuran) and the resulting solution was stirred at room temperature for 70 hours. The mixture was diluted with ethyl acetate and water and the organic layer was separated, dried over magnesium sulfate, filtered and the filtrate was concentrated in vacuo to give a white solid. This solid was recrystallized from ethyl acetate and heptane to give 4-(benzyloxy)-N- methylbenzamide as white needles (850 mg).
	With thionyl chloride
	With thionyl chloride for 2h; Reflux;
	With thionyl chloride; N,N-dimethyl-formamide In chloroform at 90℃; for 1h;	2-(4-(benzyloxy)phenyl)-6-methoxy-4H-benzo[1,3]oxazin-4-one (1). 4-(Benzyloxy)benzoic acid (0.5 g, 2.19 mmol) was dissolved in 3 mL of anhydrous chloroform to which 2 drops of anhydrous DMF was added followed by thionyl chloride (2.4 mL, 33 mmol). The resultant mixture was then heated to 90°C for 60 minutes at which time consumption of the starting material was evident. After cooling to room temperature the reaction was concentrated to dryness to yield the crude acid chloride which was used directly in the next step by dissolving it in 4 mL of anhydrous chloroform and cooling it to 0 °C. 2-amino-5-methoxybenzoic acid (0.167 g, 1.0 mmol) and triethylamine (0.38 mL, 3.0 mmol) were then added and the solution was gradually allowed to warm to room temperature overnight. The mixture was then concentrated and partitioned between 75 mL of dichloromethane and 75 mL of water. The water layer was washed with a further 2 x 50 mL of dichloromethane. After combining the organic fractions they were further washed with saturated K2CO3, 1N HCl and brine. Sodium sulfate was then added to the organic layer and after filtration concentrated to dryness under reduced pressure to yield a yellow solid. The solid was purified via silica gel column chromatography with dichloromethane to yield a white solid in 62 % yield. 1H-NMR (CDCl3, 300 MHz) δ: 8.21 (d, J = 6.9 Hz, 2H), 7.57 (d, J = 2.7 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.46-7.34 (m, 6H), 7.06 (d, J = 7.0 Hz, 2H), 5.13 (s, 2H), 3.90 (s, 3H).MS (EI) for C22H17NO4: [M+] Calc. 359.1, found 359.2. m.p. 148-149 °C
	at 0 - 20℃; Inert atmosphere;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0℃; for 2h;
	With thionyl chloride Reflux;
	With thionyl chloride for 3h; Reflux;	6.2.5 General procedure for the synthesis of 15a-g General procedure: Thionyl chloride (10 mL) was added to carboxylic acids (0.381 mmol). The mixture was stirred and refluxed for 3 h. After cooling to room temperature, the thionyl chloride was evaporated under reduced pressure giving light yellow oil or solid. The purity of 15a-g was quite sufficient to use the product directly for the following synthesis.
	With thionyl chloride In tetrahydrofuran at 20℃; for 24h; Inert atmosphere;	5.1.2 Synthesis of benzoyl chlorides General procedure: The corresponding benzoic acids were converted into benzoyl chlorides using thionylchloride as a halogenating agent, and the reaction was performed with each of the corresponding benzoic acids (6-10mmol) and 5mL of thionyl chloride using dry THF as a solvent, under a nitrogen atmosphere. The mixture was maintained at room temperature for 24h, and then the solvent, excess reagents and remaining HCl and SO2 were evaporated under vacuum. The unpurified benzoyl chloride was used immediately for the next reaction.
	With thionyl chloride; N,N-dimethyl-formamide In tetrahydrofuran at 20℃; for 12h;	Preparation of arylcarbonyl chlorides (2a-f) General procedure: Preparation of arylcarbonyl chlorides (2a-f): Arylcarboxylic acids (1a-f) weresuspended in dry THF at room temperature. Thionyl chloride and DMF wereadded dropwise. The reaction mixtures were stirred for 12 h at roomtemperature and then evaporated to dryness. The residues were useddirectly in the next step without purification.
	With thionyl chloride Reflux;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0℃; for 18h;	A stirred suspension of 4-(benzyloxy)benzoic acid (CAS1486-51-7, Aldrich 512354, 5 g, 21.91 mmol) and N,N-dimethylformamide (0.254 mL, 3.29 mmol) in dichloromethane (50 mL) was chilled to 0° C. To this stirred mixture was added dropwise oxalyl chloride (3.84 mL, 43.9 mmol). The reaction mixture was stirred for 18 hours, while slowly warming to ambient temperature. Volatiles were removed under reduced pressure to give a white solid (5.3 g, 98%). 1H NMR (300 MHz, CDCl3) δ 8.11-8.05 (m, 2H), 7.45-7.32 (m, 5H), 7.06-7.01 (m, 2H), 5.16 (s, 2H). This crude material was used without further purification by adding CH2Cl2 (70 mL) and N,O-dimethylhydroxylamine hydrochloride (2.51 g, 25.8 mmol). The reaction mixture was cooled to 0° C. and treated dropwise with Et3N (8.98 mL, 64.4 mmol). After 1 h at 0° C., the mixture was stirred at room temperature (RT) for 18 h. The reaction mixture was filtered free of insoluble salts, washed with dilute aqueous HCl, then with dilute aqueous sodium carbonate, and dried over MgSO4. Drying agent was removed by filtration and the filtrate was concentrated under reduced pressure to give a white solid (5.45 g, 93%). 1H NMR (300 MHz, methanol-d4) δ 7.69-7.62 (m, 2H), 7.47-7.27 (m, 5H), 7.07-7.01 (m, 2H), 5.13 (s, 2H), 3.58 (s, 3H), 3.33 (s, 3H). MS (DCI-NH3) m/z=272 (M+H)+, m/z=289 (M+NH4)+.
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; Inert atmosphere;
	With thionyl chloride for 1h; Reflux;
	With pyridine; thionyl chloride In toluene at 72℃; for 6h;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 1.5h; Inert atmosphere;
	With thionyl chloride; N,N-dimethyl-formamide for 4h; Reflux;
	With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 0℃; for 1h; Inert atmosphere;
	With thionyl chloride In toluene for 5h; Reflux;
	With oxalyl dichloride In dichloromethane at 20℃; for 2h;	1.1a Oxalyl chloride (8.7 mL, 99.7 mmol) and several drops ofN,N-dimethylformaldehyde (hereinafter DMF) were added to a solution of dichloromethane (40 mL) containing 4-benzyloxybenzoic acid (11.1 g, 48.6 mmol) under ice-cooling. The mixture was stirred at room temperature for 2 hours, and then the solvent was evaporated. The resulting residue was dissolved in dichloromethane (100 mL), and then glycine tert-butyl ester hydrochloride (8.20 g, 48.9 mmol) and N-ethyl-N,N-diisopropylamine (21 mL, 120 mmol) were added thereto under ice-cooling. The mixture was stirred at room temperature for 19 hours, and then water was added thereto to terminate the reaction. The mixture was extracted with dichloromethane twice, and the organic layers were combined and concentrated. The resulting residue was purified by silica gel column chromatography (hexane : ethyl acetate, 9:1 to 2:1, v/v) to give N-[4-(benzyloxy)benzoyl]glycine tert-butyl ester. All the given ester was dissolved in methanol (165 mL), and 20% palladium hydroxide-carbon (926 mg) was added thereto. The mixture was vigorously stirred under a hydrogen atmosphere at room temperature for 3.5 hours. The reaction mixture was filtered through Celite and then concentrated to give 12.2 g of the title compound (colorless crystalline solid, yield: quantitative). 1H-nuclear magnetic resonance spectrum (400 MHz, DMSO-d6) δ ppm: 9.97 (1H, s), 8.54 (1H, brt, J=6Hz), 7.70 (2H, d, J=9Hz), 6.78 (2H, d, J=9Hz), 3.83 (2H, d, J=6Hz), 1.41 (9H,s).
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 25℃; for 2h;	218.2; 220.2 Step-2: 2-O-(4-Benzyloxy-benzoyl)-6-(t-butyl-dimethyl-silyloxy)-3,4-O- isopropylidene-methyl-β-D-galactopyranoside To 4-benzyloxybenzoic acid (2.5 g. 10.95 mmol) in CH2CI2(30 mL) at 0°C, oxalyl chloride (1 .9 mL, 21.90 mmol) was added followed by a catalytic amount of N,N- dimethylformamide (0.5 mL) and the mixture stirred at 25°C for 2 h. The reaction mixture was concentrated under reduced pressure resulting in the formation of corresponding acid chloride.
	With thionyl chloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 12h; Schlenk technique; Inert atmosphere;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; Inert atmosphere;	4-(Benzyloxy)-N-(3-bromophenyl)benzamide In an inert gas atmosphere a solution of 4-benzyloxy benzoic acid (1.14 g, 5.00 mmol, 1.00 equiv) in anhydrous DCM (30 mL) was cooled to 0 °C and treated with anhydrous DMF (75 µL) and oxalyl chloride (0.64 mL, 947 mg, 5.50 mmol 1.10 equiv). After complete addition, the solution was stirred at room temperature until no further formation of gas was observed. Under reduced pressure the solution was concentrated to a volume of 10 mL and slowly added to a solution of 3-bromoaniline (0.60 mL, 946 mg, 5.50 mmol, 1.10 equiv) and pyridine (1.21 mL, 1.19 g, 15.00 mmol, 3.00 equiv) in anhydrous THF under inert gas at 0 °C. After complete addition the reaction mixture was stirred at room temperature for 3 h, then freed from solvent under reduced pressure. Purification of the residue by silica gel column chromatography (cyclohexane/EtOAc 2:1) yielded the product as colourless solid (816 mg, 2.13 mmol, 43%)
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 2h;	4-Benzyloxybenzoic acid (149 mg, 0.72 mmol) was dissolved in CH2Cl2 (10 ml). Oxalyl chloride (68 µl, 0.78 mmol) and catalytic amount of DMF was added at 0 oC, and the mixture was stirred 2 h at room temperature. Solvents were evaporated in vacuum. Methyl 4-amino-3-(cyclopropylamino)benzoate10 (175 mg, 0.85 mmol) was dissolved in CH2Cl2 (4 ml) and Et3N (365 µl, 2.61 mmol), and the crude 4-benzyloxybenzoyl chloride derivative in CH2Cl2 (6 ml) was added at room temperature and stirred for 2 h at room temperature. The reaction mixture was evaporated and quenched by addition of sat.NH4Cl. The mixture was extracted with EtOAc, and organic layer was washed successively with H2O and brine, dried over MgSO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 21a in 45 % yield.
	With pyridine; oxalyl dichloride
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 2.16667h;	1.A Part A: in situ preparation of 4-(benzyloxy)benzoyl chloride A reactor was charged with 4-(benzyloxy)benzoic acid (161.4 g) and DCM (10V), and N,N-dimethylformamide (0.1 eq) was added. Oxalyl chloride (1.4 eq) was slowly added over about 30 min and the reaction was stirred at ambient temperature for about 100 min. The solution was concentrated to ~50% of its original volume and fresh DCM (10V) was charged. The solution was concentrated to ~33% of its original volume and fresh DCM was charged to bring the preparation to its original volume, and the solution was cooled to 0- 5 °C under an inert atmosphere of nitrogen. This DCM solution of the title product was used immediately in the following procedure.
	With thionyl chloride In 1,2-dichloro-ethane at 50℃;
	With thionyl chloride Reflux;	5.1.18. General procedure 2 for preparation of 64-81, 83-91 General procedure: To a solution of organic acids (1.1 eq) in SOCl2, the reaction wasstirred at reflux, then finished, SOCl2 was removed and 5 mL THFwas added and dropwise to compound 26 (1.0 eq). Mixture wasstirred at r.t overnight. Then solvent was removed, H2O and ethylacetate was added, organic layer was dried by anhydrous Na2SO4and concentrated. Next, to a solution of compounds gained above inethyl acetate, HCl gas was added for 0.5 h, filtered the solid to affordproducts.
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane Inert atmosphere;
	With thionyl chloride In toluene for 3h; Reflux;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere;

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[ 32122-11-5 ]
[ 1486-51-7 ]

Yield	Reaction Conditions	Operation in experiment
98%	Stage #1: 4-benzyloxy-benzoic acid methyl ester With potassium hydroxide In ethanol for 10h; Reflux; Stage #2: With hydrogenchloride In ethanol; water
95%	With water; sodium hydroxide In methanol at 65℃; for 3h;	17.2 4-(benzyloxy)benzoic acid. 4-(benzyloxy)benzoic acid. Sodium hydroxide (1.80 g, 45 mmol) was added to a solution of methyl 4-(benzyloxy)benzoate (2.18 g, 9 mmol) in methanol (5 mL) and water (10 mL). The reaction mixture was stirred at 65°C for 3 hours. After the reaction, the solvent was removed in vacuo. 3N hydrochloric acid was added to make pH 2, and the product was extracted with dichloromethane (100 mL x 3). The combined organics phase was washed with brine (20 mL x 3), dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give 4-(benzyloxy)benzoic acid (1.95 g, 95%). LRMS (M + H+) m/z: calcd 227.08; found 227.
95%	With sodium hydroxide In methanol at 65℃; for 3h;	17 4-(benzyloxy)benzoic acid Sodium hydroxide (1.80 g, 45 mmol) was added to a solution of methyl 4-(benzyloxy)benzoate (2.18 g, 9 mmol) in methanol (5 mL) and water (10 mL). The reaction mixture was stirred at 65° C. for 3 hours. After the reaction, the solvent was removed in vacuo. 3N hydrochloric acid was added to make pH 2, and the product was extracted with dichloromethane (100 mL×3). The combined organics phase was washed with brine (20 mL×3), dried over anhydrous sodium sulfate, and the solvent was evaporated to dryness to give 4-(benzyloxy)benzoic acid (1.95 g, 95%). LRMS (M+H+) m/z: calcd 227.08. found 227.

92%	Stage #1: 4-benzyloxy-benzoic acid methyl ester With water; sodium hydroxide In tetrahydrofuran; methanol at 50 - 55℃; for 3h; Stage #2: With hydrogenchloride In water	C.1.II 4-Benzyloxy-benzoic acid methyl ester (8.0 g, 0.033mol) was dissolved in THF: methanol: water (3:2:1, 80ml) and NaOH (1.98g, 0.05mol) was added to the reaction mixture and stirred at 50-55 0C for 3 hours. Solvents were removed and residue was diluted with water, washed with hexane and acidified with dil HCl to obtain 4- benzyloxy-benzoic acid (7.0 g, 92 %) as a white solid.'HNMR(400MHz, CDCl3): δ 5.14 (s, 2H); 7.02 (d, J=8.8Hz, 2H); 7.4-7.42 (m, 5H); 8.05 (d, J=8.8Hz, 2H).
89%	Stage #1: 4-benzyloxy-benzoic acid methyl ester With water; sodium hydroxide In tetrahydrofuran; methanol at 50 - 55℃; for 3h; Stage #2: With hydrogenchloride In water	15 Preparation of 4-benzyloxy-benzoic acidThe above product (19.0g, 0.074mol) was dissolved in a mixture of solvents THF:methanol: water (3:2:1,250ml) and NaOH (5.9 grn, 0.15mol) was added to the reactionmixture and stirred at 50-55 C for 3 hours. Solvents were removed and the residue wasdiluted with water (20 ml), washed with hexane (2 x 50 ml) and acidified with dil. HC1 to5 obtain white precipitate, 4-benzyloxy-benzoic acid (15 g, 89 %).1HNMR(400MHz, CDC13): 8 5.14 (s, 2H); 7.02 (d, J=8.8Hz, 2H); 7.4-7.42 (m, 5H); 8.05(d, J=8.8Hz, 2H).
89%	Stage #1: 4-benzyloxy-benzoic acid methyl ester With water; sodium hydroxide In tetrahydrofuran; methanol at 50 - 55℃; for 3h; Stage #2: With hydrogenchloride In water	15 Preparation of 4-benzyloxy-benzoic acid Preparation of 4-benzyloxy-benzoic acid The above product (19.0 g, 0.074 mol) was dissolved in a mixture of solvents THF:methanol:water (3:2:1, 250 ml) and NaOH (5.9 gm, 0.15 mol) was added to the reaction mixture and stirred at 50-55° C. for 3 hours. Solvents were removed and the residue was diluted with water (20 ml), washed with hexane (2*50 ml) and acidified with dil. HCl to obtain white precipitate, 4-benzyloxy-benzoic acid (15 g, 89%). 1HNMR (400 MHz, CDCl3): δ 5.14 (s, 2H); 7.02 (d, J=8.8 Hz, 2H); 7.4-7.42 (m, 5H); 8.05 (d, J=8.8 Hz, 2H).
85%	Stage #1: 4-benzyloxy-benzoic acid methyl ester With water; sodium hydroxide In methanol at 75℃; for 2h; Stage #2: With hydrogenchloride In water
85%	With potassium hydroxide In 1,4-dioxane; methanol at 85℃; for 2h;	3,4-bis(Benzyloxy)benzoic acid (45) [51]; General procedure: Methyl 3,4-dihydroxybenzoate (2.5 g, 15 mmol) and K2CO3(8.2 g, 60 mmol) and KI (2.0 g, 12 mmol) in 100 mL of acetone was stirred at rt. The reaction suspensionwas slowly added BnCl (4.2 mL, 36 mmol) and refluxed for 7 h. TLC indicated full conversion of thestart material, added MeOH and stirred 1 h. The reaction mixture was filtered by celite and filtrate wasevaporated under reduced pressure. The residue was purified by recrystallization with hexane, and themother liquid was purified by C.C (Hex/EtOAc = 100/1-4/1) to aord methyl ester of 45 (total 5.0 g,97%) as a white solid. Further on, methyl ester of 45 (3.0 g, 9.0 mmol), KOH (5.0 g, 90 mmol) in90 mL of 1,4-dioxane and 30 mL of MeOH was stirred at 85 °C for 2 h. TLC indicated full conversionof the start material, the reaction mixture was cooled to 0 C and slowly added 6 M HCl until pH = 1.The precipitating muddy suspension was filtrated, and the white residue was washed by water andMeOH until pH = 7. The white solid was dried in vacuo, purified by recrystallizing with MeOHto obtain desired compound 45 (2.4 g, 79%) as colorless needles.
	With potassium hydroxide
	With base In tetrahydrofuran; ethanol for 24h; Heating;
	With sodium hydroxide In 1,4-dioxane Heating;
	With lithium hydroxide In tetrahydrofuran for 5h; Heating;
	With hydrogenchloride; sodium hydroxide In methanol	13 4-Benzyloxybenzoic acid EXAMPLE 13 4-Benzyloxybenzoic acid To a suspension of 15.0 g of methyl 4-benzyloxybenzoate in 225 ml of methanol were added 18.6 ml of a 5N solution of sodium hydroxide. The mixture was heated at reflux for 18 hours. The solution was cooled to room temperature and acidified to pH 3 by addition of 6N hydrochloric acid. The resulting white precipitate was filtered to give 13.6 g of the title compound: 300-MHz 1 H NMR (DMSO-d6) δ5.18 (s, 2 H), 7.04 (d, J=9 Hz, 2 H), 7.26-7.49 (m, 5 H), 7.86 (d, J=9 Hz, 2 H), 12.3 (b s, 1 H).
	Stage #1: 4-benzyloxy-benzoic acid methyl ester With sodium hydroxide; water In tetrahydrofuran at 64℃; for 4h; Stage #2: With hydrogenchloride In tetrahydrofuran; water	26 [0777] To a solution of methyl 4-(benzyloxy)benzoate (7.29 g, 30.09 mmol) in THF was added an aqueous solution of sodium hydroxide (12.0 g, 30 0 mmol/ 50 mL). The reaction mixture was heated to 64°C for 4 h. After completion of the reaction (as monitored by LC/MS), the reaction mixture was neutralized with 3N aqueous HCl. The product (6.79 g) was collected by filtration.
	Stage #1: 4-benzyloxy-benzoic acid methyl ester With water; potassium hydroxide In methanol at 64℃; for 6h; Stage #2: With hydrogenchloride In water Cooling with ice;	23.2 Step 2: Methyl 4-(benzyloxy)benzoate (6.99 g, 28.9 mmol) was dissolved in methanol (100 mL) and a 30% aqueous solution of potassium hydroxide (20 mL) was added and heated at 64 0C for 6 h. The solvent was evaporated and the crude mixture was treated with ice water (250 mL). The pH was adjusted to 1 with the addition of 6 N HCI. The precipitate was collected on filter paper via vacuum filtration. The white solid was dried on a vacuum pump overnight to provide 4-(benzyloxy)benzoic acid as a white solid. MS (ES) m/z 229.0 ([M+H]+).
	With water; potassium hydroxide for 1h; Reflux;	5.1.1 Synthesis of benzyloxy derivatives General procedure: 6-Hydroxybenzoic acid and 6-hydroxynicotinic acid were previously transformed in their corresponding methyl esters, using methanol-sulfuric acid under reflux by 5days. Methyl esters were benzylated using benzyl chloride in acetonitrile as solvent and NaHCO3, the mixture was kept under reflux for 3days. After this time, the solvent was evaporated and the benzyloxy esters were hydrolyzed in KOH by refluxing for 1h. benzyloxy acids were purified by column chromatography using Silica gel 60 and a mobile phase of CHCl3/CH3OH (90/10).
	Stage #1: 4-benzyloxy-benzoic acid methyl ester In tetrahydrofuran; water Inert atmosphere; Alkaline conditions; Stage #2: With hydrogenchloride In tetrahydrofuran; water Inert atmosphere;
	With water; potassium hydroxide In ethanol for 1h; Reflux;
	With methanol; potassium hydroxide
23.9 g	With sodium hydroxide In tetrahydrofuran; methanol; water at 80℃; for 1h;	4-Benzyloxybenzoic acid (9a) To a solution of 8a (15.0 g, 0.109 mol) in MeOH (360 mL) was added SOCl2 (7.90 mL, 0.109 mol) fordropwise at 60 °C. After stirring at 60 °C for 5 h, the reaction mixture was evaporated under reducedpressure. The crude mixture was applied to following reaction without further purification.To a mixture of crude residue and K2CO3 (45.2 g, 0.329 mol) in DMF (182 mL) was added benzylbromide (19.4 mL, 0.163 mol) at 100 °C. The reaction mixture was stirred at 100 °C for 16 h. Then, thereaction mixture was filtered through a pad of Celite, diluted with H2O, and extracted with CH2Cl2. Theorganic layer was washed with water followed by brine, dried over anhydrous MgSO4, and evaporatedunder reduced pressure. The crude residue was applied to following reaction without further purification. To a stirred solution of crude residue in MeOH/THF (1/1, 360 mL) was added 4 M NaOH aq. (90 mL,0.36 mol) at 80 °C. The reaction mixture was stirred at 80 °C for 1 h. Then, the reaction mixture wasquenched with 6 M HCl aq., and filtered. The filtrate was washed with H2O to give 9a (23.9 g, 0.104 mol,96%) as a white solid.
	With water; sodium hydroxide In ethanol for 2h; Reflux;
	With sodium hydroxide In 1,4-dioxane; methanol; water Reflux;
	With water; sodium hydroxide In ethanol for 2h; Reflux;
	With sodium hydroxide In ethanol
2.69 g	With water; sodium hydroxide In 1,4-dioxane; methanol at 120℃;	1.3 Step 3. Add compound 1c (14.88mmol) to a mixed solution of methanol (MeOH, 20mL), dioxane (40mL) and H2O (15mL), then add NaOH (0.50mol), stir the reaction overnight, and the reaction mixture The reaction was refluxed at 120°C overnight, concentrated under reduced pressure to remove the solvent, and then the residue was extracted with DCM. The organic layer was washed with saturated brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to obtain compound 1d (2.69g);

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[16]Faundez-Parraguez, Manuel; Farias-Rabelo, Nicolas; Gonzalez-Gutierrez, Juan Pablo; Etcheverry-Berrios, Alvaro; Alzate-Morales, Jans; Adasme-Carreño, Francisco; Varas, Rodrigo; Bermudez, Isabel; Iturriaga-Vasquez, Patricio [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 10, p. 2687 - 2694]
[17]Deberardinis, Albert M.; Madden, Daniel J.; Banerjee, Upasana; Sail, Vibhavari; Raccuia, Daniel S.; De Carlo, Daniel; Lemieux, Steven M.; Meares, Adam; Hadden, M. Kyle [Journal of Medicinal Chemistry, 2014, vol. 57, # 9, p. 3724 - 3736]
[18]Siva Mohan Reddy; Narasimhaswamy; Mohana Raju [New Journal of Chemistry, 2014, vol. 38, # 9, p. 4357 - 4364]
[19]Orlowska, Ewelina; Roller, Alexander; Wiesinger, Hubert; Pignitter, Marc; Jirsa, Franz; Krachler, Regina; Kandioller, Wolfgang; Keppler, Bernhard K. [RSC Advances, 2016, vol. 6, # 46, p. 40238 - 40249]
[20]Hiza, Aiki; Tsukaguchi, Yuta; Ogawa, Takahiro; Inai, Makoto; Asakawa, Tomohiro; Hamashima, Yoshitaka; Kan, Toshiyuki [Heterocycles, 2014, vol. 8, # 2, p. 1371 - 1396]
[21]Bajzíková, Kvetoslava; Svoboda, Jiří; Novotná, Vladimíra; Pociecha, Damian; Gorecka, Ewa [New Journal of Chemistry, 2017, vol. 41, # 11, p. 4672 - 4679]
[22]Li, Haiwei; Li, Man; Xu, Renyang; Wang, Shouxin; Zhang, Yongmin; Zhang, Lihe; Zhou, Demin; Xiao, Sulong [European Journal of Medicinal Chemistry, 2019, vol. 163, p. 560 - 568]
[23]Sun, Chiyu; Zhang, Ying; Wang, Han; Yin, Zhengxu; Wu, Lingqiong; Huang, Yanmiao; Zhang, Wenhu; Wang, Youbing; Hu, Qibo [Chemical Biology and Drug Design, 2021, vol. 97, # 3, p. 546 - 552]
[24]Cigl, Martin; Hamplová, Věra; Novotná, Vladimíra; Pociecha, Damian; Podoliak, Natalia [Journal of Molecular Liquids, 2021, vol. 336]
[25]Current Patent Assignee: KUNMING UNIVERSITY OF SCIENCE AND TECHNOLOGY - CN113173857, 2021, A Location in patent: Paragraph 0027; 0035; 0039

3
[ 56441-55-5 ]
[ 1486-51-7 ]

Yield	Reaction Conditions	Operation in experiment
93%	With potassium hydroxide In ethanol for 4h; Heating;
90%	With lithium hydroxide monohydrate; sodium hydroxide In ethanol for 17h; Reflux;
	With potassium hydroxide

	With potassium hydroxide
	With sodium hydroxide
	With hydroxide
	With lithium hydroxide monohydrate
	With potassium hydroxide In methanol; lithium hydroxide monohydrate; ethyl acetate	1 4-Benzyloxybenzoic acid (12) 4-Benzyloxybenzoic acid (12) To the solution of 0.5 g KOH in 40 ml MeOH, was added 6.5 mmol of ethyl 4-benzyloxybenzoate. After the resulting mixture was refluxed for 4 hrs, the excess methanol was removed. The residue was mixed with 30 ml water and extracted with ether twice. The water solution was acidified with conc. HCl and extracted with ethyl acetate. The ethyl acetate solution was washed with brine and dried. After evaporation of solvent, pure product was obtained in quantitative yield.
	With sodium hydroxide In tetrahydrofuran; ethanol; lithium hydroxide monohydrate
	With sodium hydroxide In methanol; lithium hydroxide monohydrate at 20℃;	5.2. 5-phenylisoxazole-3-carboxylic acid (AM1) General procedure: Diethyl oxalate (72.40 mmol, 10.60 g) was added to the freshlyprepared sodium ethylate solution (2.26 mol/mL, 80 mL) at 0 C andthen a solution of acetophenone (36.2 mmol, 4.35 g) in EtOH wasadded slowly. The reaction was allowed to warm to room temperatureand stirred for 8 h. The reaction was acidified with 3 mol/LHCl until the product precipitated. The precipitate was filtered anddried to afford intermediate 8.Hydroxylamine hydrochloride (54.30 mmol, 3.77 g) was addedto a solution of intermediate 8 (36.20 mmol, 7.97 g) in EtOH, andthe reaction was stirred at reflux condition. When the reaction wascomplete, the organic solvent was removed under reduced pressureand the residues were dissolved in water. The mixture wasextracted with ethyl acetate three times and the combined extractwas dried, concentrated and purified to afford intermediate 9.To a solution of intermediate 9 (10.0 mmol, 2.17 g) in MeOH(50 mL), NaOH (2 mol/L, 20 mL)was added. The reactionwas stirredat room temperature and monitored by TLC. The organic solventwas removed in vacuo and the residues were dissolved inwater. Themixture was acidified with 2 mol/L HCl until the product precipitated.The precipitate was filtered and dried to afford intermediateAM1.

Reference： [1]Lam, Jacky W.Y.; Dong, Yuping; Cheuk, Kevin K.L.; Tang, Ben Zhong [Macromolecules, 2003, vol. 36, # 21, p. 7927 - 7938]
[2]Pradhan, Balaram; Chakraborty, Nirmalangshu; Gupta, Ravindra Kumar; Shanker; Achalkumar, Ammathnadu S. [New Journal of Chemistry, 2017, vol. 41, # 2, p. 879 - 888]
[3]Tseng [Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1935, vol. 55, p. 132,141; engl. Ref. S. 30, 35][Chem.Abstr., 1935, p. 7981]
[4]Current Patent Assignee: BAYER AG - DE407669, 1924, C [Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 14, p. 1371][Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 14, p. 1371]
[5]Baggaley; Fears; Hindley; Morgan; Murrell; Thorne [Journal of Medicinal Chemistry, 1977, vol. 20, # 11, p. 1388 - 1393]
[6]Kasthuraiah [Journal of Materials Chemistry, 1996, vol. 6, # 10, p. 1619 - 1625]
[7]Shubashree; Sadashiva; Dhara, Surajit [Molecular Crystals and Liquid Crystals Science and Technology, Section A: Molecular Crystals and Liquid Crystals, 2002, vol. 381, p. 21 - 32]
[8]Current Patent Assignee: CITIZEN WATCH CO LTD - US2003/17278, 2003, A1
[9]Sleebs, Brad E.; Jarman, Kate E.; Frolich, Sonja; Wong, Wilson; Healer, Julie; Dai, Weiwen; Lucet, Isabelle S.; Wilson, Danny W.; Cowman, Alan F. [International Journal for Parasitology: Drugs and Drug Resistance, 2020, vol. 14, p. 188 - 200]
[10]Cheng, Maosheng; Su, Xin; Sun, Nannan; Sun, Yin; Tian, Linfeng; Yin, Wenbo; Zhang, Chu; Zhao, Dongmei; Zhao, Liyu; Zhao, Shizhen; Zheng, Yang [European Journal of Medicinal Chemistry, 2022, vol. 228]

4
[ 100-44-7 ]
[ 99-96-7 ]
[ 1486-51-7 ]

Yield	Reaction Conditions	Operation in experiment
90%	With n-Bu₄POH In tetrahydrofuran; water at 0 - 20℃;
	With sodium hydroxide
	With sodium hydroxide; sodium hydride 1.a) DMF; 2.) MeOH, H₂O; Yield given. Multistep reaction;

	With hydrogenchloride; sodium hydroxide; potassium carbonate In ethanol; water; acetone	1.1 Synthesis of 2,6,9-tris(4-hydroxybenzoyloxy)anthracene (1) A suspension of p-hydroxybenzoic acid (200 g, 1.2 mole), benzyl chloride (190 g, 1.5 mole) and potassium carbonate (165 g, 1.2 mole) in acetone (1200 ml) was reacted with stirring for 12 hours under reflux. After cooling, the precipitate was filtered off, and the filtrate was concentrated until 400 ml. H2 O (1 l) was added with stirring to the residue and the mixture was allowed to stand. The organic layer was separated, and concentrated, and the residue was added to a solution of NaOH (60 g, 1.5 mole) in H2 O (1 l) and ethanol (500 ml), followed by stirring for 4 hours to be dissolved. Then conc. hydrochloric acid (200 ml) was added to make pH 1. The precipitate was filtered, washed with H2 O and with ethanol, and dried to give 195 g of 4-benzyloxybenzoic acid as white crystals having a m.p. of 191.2°-192.6° C. 1 H-NMR δ ppm (CDCl3 /DMSO-d6): 5.10 (2H, s, ARCH2 O-), 6.92 (2H, d, J=8Hz, Ar 3-H, 5-H), 7.13-7.51 (5H, m, ArH), 7.86 (2H, d, J=8Hz, Ar 2-H, 6-H), 8.65 (1H, bs, OH). IR (KBr-disk) ν cm1: 1675 (COOH).
	With hydrogenchloride; sodium hydroxide; potassium carbonate In ethanol; water; acetone	S.1.1 Synthesis Example 1 (1) A suspension of p-hydroxybenzoic acid (200 g, 1.2 mole), benzyl chloride (190 g, 1.5 mole) and potassium carbonate (165 g, 1.2 mole) in acetone (1200 ml) was reacted with stirring for 12 hours under reflux. After cooling, the precipitate was filtered off, and the filtrate was concentrated until 400 ml. H2O (1 l) was added with stirring to the residue and the mixture was allowed to stand. The organic layer separated was concentrated. The residue was added to a solution of NaOH (60 g, 1.5 mole) in H2O (1 l) and ethanol (500 ml), and stirred for 4 hours and dissolved. Then conc. hydrochloric acid (200 ml) was added to make pH 1. The precipitate was filtered, washed with H2O and with ethanol, and dried to give 195 g of 4-benzyloxybenzoic acid as white crystals having a m.p. of 191.2-192.6°C.
	With potassium iodide; sodium hydroxide In ethanol

Reference： [1]Liu, Pingli; Huang, Liang; Faul, Margaret M. [Tetrahedron Letters, 2007, vol. 48, # 41, p. 7380 - 7382]
[2]Cavallito; Buck [Journal of the American Chemical Society, 1943, vol. 65, p. 2140] Frieden; Winzler [Journal of Biological Chemistry, 1949, vol. 179, p. 423,425]
[3]Chiang, Long Y. [Molecular Crystals and Liquid Crystals (1969-1991), 1987, vol. 146, p. 137 - 142]
[4]Current Patent Assignee: FUJIFILM HOLDINGS CORP. - US5498748, 1996, A
[5]Current Patent Assignee: PANASONIC CORPORATION; FUJIFILM HOLDINGS CORP. - EP636941, 1995, A1
[6]Current Patent Assignee: DIC CORP. - KR101523330, 2015, B1 Location in patent: Paragraph 0043

5
[ 14938-35-3 ]
[ 1486-51-7 ]
[ 111973-82-1 ]

Reference： [1]Molecular Crystals and Liquid Crystals (1969-1991),1987,vol. 146,p. 137 - 142
[2]Journal of Chemical Physics,1990,vol. 92,p. 3917 - 3929

6
[ 1486-51-7 ]
[ 38713-56-3 ]

Yield	Reaction Conditions	Operation in experiment
82.5%	With hydrogen In ethanol at 40℃; for 2h;
	Multi-step reaction with 2 steps 1: Ph₃P; diisopropyl azodicarboxylate / tetrahydrofuran / 2 h / 20 °C 2: H₂; AcOH / Pd(OH)2/C / ethyl acetate / 12 h
	Multi-step reaction with 2 steps 1: PPh₃; diisopropyl azodicarboxylate / tetrahydrofuran / 20 °C 2: H₂; AcOH / Pd(OH)2/C / ethyl acetate

Multi-step reaction with 2 steps 1: 34 percent / benzene; dimethylformamide 2: 65.4 percent / H₂ / hydrogenation catalyst

Reference： [1]Neubert, M. E.; Leung, K.; Jirousek, M. R.; Ezenylimba, M. C.; Sabol-Keast, S.; et al. [Molecular Crystals and Liquid Crystals (1969-1991), 1991, vol. 197, p. 21 - 41]
[2]Nihei, Ken-Ichi; Nihei, Atsuko; Kubo, Isao [Journal of Agricultural and Food Chemistry, 2004, vol. 52, # 16, p. 5011 - 5020]
[3]Nihei, Ken-Ichi; Nihei, Atsuko; Kubo, Isao [Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 22, p. 3993 - 3996]
[4]Neubert, M. E.; Keast, S. S.; Ezenyilimba, M. C.; Greer, P. B.; Jones, W. C.; et al. [Molecular Crystals and Liquid Crystals Science and Technology, Section A: Molecular Crystals and Liquid Crystals, 1993, vol. 237, p. 47 - 68]

7
[ 1486-51-7 ]
[ 99-96-7 ]

Yield	Reaction Conditions	Operation in experiment
99%	With 10% Pd/C; cyclohexa-1,4-diene In ethyl acetate at 100℃; for 0.5h; Microwave irradiation;
99%	With palladium diacetate; sodium hydride In N,N-dimethyl acetamide at 25℃; for 3h; Inert atmosphere;
99%	With palladium diacetate; sodium hydride In N,N-dimethyl acetamide at 50℃; for 5h; Inert atmosphere;	18 Under the protection of nitrogen, palladium acetate (3.4 mg, 0 . 015 mmol, 5 mol %) and sodium hydride (60% in oil, 36 mg, 0.90 mmol, 3.0 equiv) suspension for DMA (1.0 ml), 25 °C stirring 5 minutes, adding compound 15 (0.3 mmol) in DMA (0.5 ml) solution, then in 50 °C reaction 5 hours, adding ice water stopped reaction, dilute hydrochloric acid for adjusting the pH value to 3.5, extracted with ethyl acetate, the combined extract, sulfate to dry, dry [...], column chromatography purification, to obtain the product 16, yield 99%.

93%	With Pd⁽⁰⁾EnCat; ammonium formate In N,N-dimethyl-formamide at 80℃; for 0.166667h; Irradiation; microwave;
85%	With triethylammonium formate for 1h; Ambient temperature;

Reference： [1]Location in patent: scheme or table Quinn, John F.; Razzano, Dana A.; Golden, Kathryn C.; Gregg, Brian T. [Tetrahedron Letters, 2008, vol. 49, # 42, p. 6137 - 6140]
[2]Mao, Yujian; Liu, Ye; Hu, Yanwei; Wang, Liang; Zhang, Shilei; Wang, Wei [ACS Catalysis, 2018, vol. 8, # 4, p. 3016 - 3020]
[3]Current Patent Assignee: SOOCHOW UNIVERSITY (SUZHOU) - CN108358760, 2018, A Location in patent: Paragraph 0041
[4]Quai, Monica; Repetto, Claudio; Barbaglia, Walter; Cereda, Enzo [Tetrahedron Letters, 2007, vol. 48, # 7, p. 1241 - 1245]
[5]Krishnamurty, H. G.; Ghosh, Sanjukta; Sathyanarayana, S. [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1986, vol. 25, p. 1253 - 1254]

8
[ 56442-22-9 ]
[ 1486-51-7 ]

Yield	Reaction Conditions	Operation in experiment
99%	With potassium hydroxide In ethanol; water for 4h; Heating;
94%	With potassium hydroxide In methanol Heating;
91%	With potassium hydroxide In methanol; water for 6h; Heating;

91%	With potassium hydroxide In methanol; water for 6h; Heating;
87%	With potassium hydroxide In methanol; water Reflux;
84%	With methanol; sodium tetrahydroborate; nickel(II) chloride hexahydrate at 20℃; for 1h; chemoselective reaction;
80%	With potassium hydroxide In ethanol; water for 1h; Heating;
80%	With sodium hydroxide In methanol for 1h; Reflux;
78%	With sodium hydroxide In ethanol for 6h; Heating;
78.95%	With sodium hydroxide In tetrahydrofuran at 50℃;	Compound 2a (1.85 g mmol, 5.81 mmol) was dissolved intetrahydrofuran (10 mL), and 6 mol/L NaOH solution(30 mL) was added. The mixture was stirred at 50 °C.After the reaction was complete, the solvent was removedunder reduced pressure, and the residue was adjusted to acidto precipitate white solid 3a (1.05 g). The yield was 78.95%.
	With sodium hydroxide
	With water; lithium hydroxide In tetrahydrofuran
2.06 g	Stage #1: benzyl 4-benzyloxybenzoate With sodium hydroxide In methanol; water at 20℃; Inert atmosphere; Stage #2: With hydrogenchloride In water	General procedure for preparation of acid (43b-d) General procedure: A solution of hydroxy benzoic acid (1.0 equiv), BnBr (3-5 equiv) and K2CO3 (10-15 equiv) in DMF was stirred overnight under argon. After filtration, the solution was concentrated in vacuo to afford the crude product. The crude product was dissolved in methanol and an aqueous solution of NaOH (75 equiv) was added. The mixture was stirred at room temperature overnight and the solution concentrated in vacuo to remove the methanol. The residue was acidified with 10 % HCl to pH 2 and then partitioned between ethyl acetate and water. The organic phase was washed with brine, dried (MgSO4 anh), and concentrated. The residue was purified by recrystallization from CH2CH2 / MeOH.
771 mg	With sodium hydroxide In methanol; water at 50℃; for 2h;
771 mg	With water; sodium hydroxide In methanol at 50℃; for 2h;

Reference： [1]Byron, David J.; Komitov, Lachezar; Matharu, Avtar S.; McSherry, Ian; Wilson, Robert C. [Journal of Materials Chemistry, 1996, vol. 6, # 12, p. 1871 - 1878]
[2]Fontes, Ernest; Lee, Wah Keat; Heiney, Paul A.; Nounesis, George; Garland, Carl W.; et al. [Journal of Chemical Physics, 1990, vol. 92, # 6, p. 3917 - 3929]
[3]Samosorn, Siritron; Bremner, John B.; Ball, Anthony; Lewis, Kim [Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 3, p. 857 - 865]
[4]Huo, Congde; Shi, Guoqing; Lam, Wai Har; Chen, Di; Cui, Quizhi Cindy; Dou, Q. Ping; Chan, Tak Hang [Canadian Journal of Chemistry, 2008, vol. 86, # 6, p. 495 - 502]
[5]Location in patent: scheme or table Catel, Yohann; Aladedunye, Felix; Przybylski, Roman [Journal of Agricultural and Food Chemistry, 2010, vol. 58, # 20, p. 11081 - 11089]
[6]Location in patent: experimental part Khurana, Jitender M.; Arora, Reema [Synthesis, 2009, # 7, p. 1127 - 1130]
[7]Tranchimand, Sylvain; Tron, Thierry; Gaudin, Christian; Iacazio, Gilles [Synthetic Communications, 2006, vol. 36, # 5, p. 587 - 597]
[8]Calamante, Massimo; Dei, Filippo; Maramai, Samuele; Migliorini, Francesca; Petricci, Elena [ChemCatChem, 2021, vol. 13, # 12, p. 2794 - 2806]
[9]Herbert, Richard B.; Jackson, Frederick B.; Nicolson, Ian T. [Journal of the Chemical Society. Perkin transactions I, 1984, # 4, p. 825 - 831]
[10]Xie, Yundong; Liu, Jiping; Shi, Yongheng; Bin Wang; Wang, Xiaoping; Wang, Wei; Sun, Meng; Xu, Xinya; He, Shipeng [Medicinal Chemistry Research, 2021, vol. 30, # 9, p. 1688 - 1702]
[11]Faghih, Ramin; Dwight, Wesley; Gentles, Robert; Phelan, Kathleen; Esbenshade, Timothy A; Ireland, Lynne; Miller, Thomas R; Kang, Chae-Hee; Fox, Gerard B; Gopalakrishnan, Sujatha M; Hancock, Arthur A; Bennani, Youssef L [Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 15, p. 2031 - 2034]
[12]Location in patent: scheme or table Zhang, Weihe; Liu, Yi; Chen, Xiaozhuo; Bergmeier, Stephen C. [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 7, p. 2191 - 2194]
[13]Xia, Yan; Jin, Yinglan; Kaur, Navneet; Choi, Yongseok; Lee, Kyeong [European Journal of Medicinal Chemistry, 2011, vol. 46, # 6, p. 2386 - 2396]
[14]Kühl, Nikos; Graf, Dominik; Bock, Josephine; Behnam, Mira A. M.; Leuthold, Mila-Mareen; Klein, Christian D. [Journal of Medicinal Chemistry, 2020, vol. 63, # 15, p. 8179 - 8197]
[15]Kühl, Nikos; Leuthold, Mila M.; Behnam, Mira A. M.; Klein, Christian D. [Journal of Medicinal Chemistry, 2021, vol. 64, # 8, p. 4567 - 4587]

9
[ 100-39-0 ]
[ 99-96-7 ]
[ 1486-51-7 ]

Yield	Reaction Conditions	Operation in experiment
99%	With potassium hydroxide In ethanol; water for 20h; Reflux;	Synthesis of 4-(benzyloxy)benzoic acid 84 S27 KOH and benzyl bromide were added to a solution of 4-hydroxybenzoic acid (1 eq, 4.00 g, 28.90 mmol), in EtOH:H2O 9:1 (3,54 ml . mmol/eq). The mixture was heated under reflux for 20 h. 20 % KOH solution (20 ml) was then added and the mixture was then maintained under reflux for 4 h. The mixture was then diluted with H2O (60 ml) and acidified with 20% HCl solution. The precipitate formed was filtered and washed with water and n-hexane to give the pure title compound as a white solid in 99% yield.1H-NMR (DMSO-d6), δ: 5.19 (s, 2H), 7.10 (d, J = 8.8 Hz, 2H), 7.34-7.37 (m, 1H), 7.39-7.42 (m, 2H), 7.45-7.48 (m, 2H), 7.90 (d, J = 8.8 Hz, 2H), 12.61 (bs, 1H). 13C-NMR (DMSO-d6), δ: 69.4, 114.5, 127.7, 127.9, 128.4, 131.3, 123.1, 136.5, 161.9, 166.9.
94%	With n-Bu₄POH In tetrahydrofuran; water at 0 - 20℃;
91%	With potassium hydroxide In ethanol; water for 5h; Reflux;	7; 25 Add 4-hydroxybenzoic acid (1.38g, 10mmol), potassium hydroxide (1.12g, 20mmol), ethanol (20mL), water (10mL) into a 100mL single-mouth flask, add benzyl bromide (3.42g, 20mmol) dropwise, and reflux After reacting for 5 hours, add water (30mL), adjust pH to 2.0 with concentrated hydrochloric acid, precipitate solid, filter, wash with water, wash with n-hexane, dry to obtain solid 4-benzyloxybenzoic acid (2.07g), yield 91%.

73%	With potassium hydroxide In ethanol; water for 24h; Reflux;
72%	Stage #1: benzyl bromide; 4-hydroxy-benzoic acid With potassium carbonate In N,N-dimethyl-formamide for 12h; Stage #2: With potassium hydroxide In methanol for 1h; Reflux; Stage #3: With hydrogenchloride In methanol; water	1 (5.4 g, 30 mmol) were dissolved in dry DMF and stirred for 12 h. Water was added to the reaction mixture and extracted with EtOAc thrice. The combined organic phase was evaporated and dissolved in 8N KOH in MeOH (50 mL) and refluxed for another 1 h. After completion of the reaction, the mixture was acidified with concentrated HC1 to pH 2-3. The formed precipitate was filtered, dissolved in EtOAc and washed with water, brine and dried over Na2S04. Removal of the solvent gave crude 4-benzyloxy-benzoic acid which on passing through a small pad of celite with ethyl acetate gave pure product as a white solid, m.p. 189-191°C (2.4 g, 72% yield); NMR (400 MHz, d6- Acetone) δ:-7.34 (m, 5H), 7.12 (d, 2H), 5.22 (s, 2H).
70%	With potassium hydroxide In ethanol for 24h; Heating;
47%	With sodium hydroxide for 10h; Heating;
	With sodium hydroxide In ethanol; water
	With potassium hydroxide In ethanol; water for 6h; Heating;
	With potassium hydroxide In ethanol Heating;
	With potassium hydroxide In ethanol; water for 24h; Reflux;
	With potassium carbonate In acetone Reflux;
	With potassium hydroxide In ethanol for 25h; Reflux;	6.2.4 General procedure for he synthesis of 14a-d General procedure: 4-hydrobenzoic acid (1.38 g, 10 mmol) and bromoalkane (12.5 mmol) were dissolved in ethanol (20 mL). KOH (1.23 g, 21.83 mmol) was then added and the resulting mixture was stirred under reflux for 24 h. Subsequently, KOH (1.23 g, 20.14 mmol) was added and reflux was continued for a further 1 h. After cooling to room temperature, ethanol was removed under vacuum, and the residue was resolved in water (60 mL), acidified to pH = 1 with HCl. After that, the precipitate was collected, recrystallized twice from ethanol, and finally dried under vacuum to give 14a-d (30-44%) of white solids.
38g	With tetrabutylammomium bromide; potassium iodide; sodium hydroxide In ethanol; water at 50 - 70℃; for 3h;	Stirrer, a condenser and a thermometer, the reaction vessel having a 3-(p-hydroxyphenyl)benzoic acid 33.2g (240 mmol), potassium iodide 4g, tetrabutylammonium bromide 1g, 400ml of ethanol, and the charged was stirred at room temperature.It was added dropwise a 25% aqueous solution of sodium hydroxide, 24g slowly.After the addition, maintaining the reaction vessel at 50 , and 50g was added dropwise benzyl bromide (288 mmol) slowly.After the addition was completed, the reaction vessel also by heating to 70 by further reaction for 3 hours.After completion of the reaction, neutralized with 10% hydrochloric acid and subjected to extraction with ethyl acetate and dried over sodium sulfate, the solvent was concentrated to 38g of the compound synthesized as shown in equation (1).
38 g	With tetrabutylammomium bromide; potassium iodide; sodium hydroxide In ethanol; water at 20 - 70℃; for 3h;	1 Stirrer, a reaction vessel equipped with a condenser and thermometer 3-(p-hydroxyphenyl) benzoic acid 33.2g (240 mmol), potassium iodide 4g, tetrabutylammonium bromide 1g, ethanol 400ml and the mixture was stirred at room temperature was charged a 25% aqueous solution of sodium hydroxide 24g was slowly dropped, After completion of the addition, maintaining the reaction vessel to 50°C ,benzyl bromide 50g (288 mmol) it was slowly dropped. After the addition, the mixture was allowed to react for additional 3 hours warmed further 70 ° C. the reaction vessel. After completion of the reaction, it was extracted with ethyl acetate and neutralized with 10% hydrochloric acid, dried over sodium sulfate, and the compound solvent was concentrated expressed by equation (1) and 38g synthesis.
	Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 80 °C 2: water; sodium hydroxide / methanol / 2 h / 50 °C
	With potassium hydroxide In ethanol; water Reflux;

Reference： [1]Giancotti, Gilda; Cancellieri, Michela; Balboni, Andrea; Giustiniano, Mariateresa; Novellino, Ettore; Delang, Leen; Neyts, Johan; Leyssen, Pieter; Brancale, Andrea; Bassetto, Marcella [European Journal of Medicinal Chemistry, 2018, vol. 149, p. 56 - 68]
[2]Liu, Pingli; Huang, Liang; Faul, Margaret M. [Tetrahedron Letters, 2007, vol. 48, # 41, p. 7380 - 7382]
[3]Current Patent Assignee: ZHEJIANG UNIVERSITY OF TECHNOLOGY - CN111995567, 2020, A Location in patent: Paragraph 0112-0113; 0116; 0257-0258; 0260
[4]Location in patent: scheme or table Soulage, Christophe O.; Grand, Lucie; Géloën, Alain; Chambert, Stéphane [Tetrahedron Letters, 2012, vol. 53, # 5, p. 480 - 483]
[5]Current Patent Assignee: WAYNE STATE UNIVERSITY; MCGILL UNIVERSITY; HONG KONG POLYTECHNIC UNIVERSITY - WO2012/171114, 2012, A1 Location in patent: Page/Page column 59
[6]Cativiela, Carlos; Serrano, Jose L.; Zurbano, Maria M. [Journal of Organic Chemistry, 1995, vol. 60, # 10, p. 3074 - 3083]
[7]Sakata, Kazunori; Koyanagi, Ken; Hashimoto, Mamoru [Journal of Heterocyclic Chemistry, 1995, vol. 32, # 1, p. 329 - 334]
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[10]De Givenchy, Elisabeth Taffin; Guittard, Frederic; Geribaldi, Serge [Molecular Crystals and Liquid Crystals Science and Technology, Section A: Molecular Crystals and Liquid Crystals, 2001, vol. 365, p. 91 - 98]
[11]Location in patent: experimental part Solorzano, Carlos; Antonietti, Francesca; Duranti, Andrea; Tontini, Andrea; Rivara, Silvia; Lodola, Alessio; Vacondio, Federica; Tarzia, Giorgio; Piomelli, Daniele; Mor, Marco [Journal of Medicinal Chemistry, 2010, vol. 53, # 15, p. 5770 - 5781]
[12]Location in patent: scheme or table Yuan, Lei; Li, Yanchun; Zou, Chunyang; Wang, Chao; Gao, Jian; Miao, Caixia; Ma, Enlong; Sun, Tiemin [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 6, p. 2216 - 2220]
[13]Zhang, Mingming; Zhu, Weiliang; Li, Yingxia [European Journal of Medicinal Chemistry, 2013, vol. 62, p. 301 - 310]
[14]Current Patent Assignee: DIC CORP. - KR101523330, 2015, B1 Location in patent: Paragraph 0101; 0102
[15]Current Patent Assignee: DIC CORP. - JP5962945, 2016, B2 Location in patent: Paragraph 0088
[16]Kühl, Nikos; Leuthold, Mila M.; Behnam, Mira A. M.; Klein, Christian D. [Journal of Medicinal Chemistry, 2021, vol. 64, # 8, p. 4567 - 4587]
[17]Jiang, Xiaoying; Guo, Jianan; Zhang, Changjun; Gu, Jinping; Zhou, Tao; Bai, Renren; Xie, Yuanyuan [Journal of Enzyme Inhibition and Medicinal Chemistry, 2021, vol. 36, # 1, p. 2045 - 2054]

10
[ 1486-51-7 ]
C₄₄H₄₄O₈SSi [ No CAS ]
4-Benzyloxy-benzoic acid (2S,3R,4S,5R,6R)-3,4,5-tris-benzoyloxy-6-(tert-butyl-diphenyl-silanyloxymethyl)-tetrahydro-pyran-2-yl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With N-iodo-succinimide; trifluorormethanesulfonic acid In dichloromethane at 25℃; for 2h;

Reference： [1]Nicolaou; Watanabe, Nobuhide; Li, Jim; Pastor, Joaquin; Winssinger, Nicolas [Angewandte Chemie - International Edition, 1998, vol. 37, # 11, p. 1559 - 1561]

11
[ 1486-51-7 ]
[ 767-00-0 ]
[ 391217-79-1 ]

Yield	Reaction Conditions	Operation in experiment
81%	With dmap; dicyclohexyl-carbodiimide In chloroform at 20℃; for 15h;
81%	With dmap; dicyclohexyl-carbodiimide In chloroform at 20℃; for 15h;
	With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 12h;

Reference： [1]Amaranatha Reddy; Sadashiva [Journal of Materials Chemistry, 2004, vol. 14, # 3, p. 310 - 319]
[2]Sadashiva; Amaranatha Reddy; Pratibha; Madhusudana [Chemical Communications, 2001, # 20, p. 2140 - 2141] Sadashiva; Amaranatha Reddy; Pratibha; Madhusudana [Journal of Materials Chemistry, 2002, vol. 12, # 4, p. 943 - 950]
[3]Srinivasa, Hosapalya Thimmaiah; Palakshamurthy, Bandrehalli Siddagangappa; Velmurugan, Devadasan; Devarajegowda, Hirihalli Chickegowda; HariPrasad, Suresh [Acta Chimica Slovenica, 2015, vol. 62, # 4, p. 768 - 774]

12
[ 1486-51-7 ]
[ 41107-82-8 ]
[ 219749-84-5 ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: p-(benzyloxy)benzoic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 24h; Stage #2: 2,5-anhydro-D-mannitol With dmap In pyridine at 50℃; for 24h; Further stages.;

Reference： [1]Laufersweiler; Rohde; Chaumette; Sarazin; Parquette [Journal of Organic Chemistry, 2001, vol. 66, # 19, p. 6440 - 6452]

13
[ 464-43-7 ]
[ 1486-51-7 ]
[(1S)-endo]-borneyl 4-benzyloxybenzoate [ No CAS ]

Reference： [1]Macromolecules,2003,vol. 36,p. 7927 - 7938

14
[ 1486-51-7 ]
[ 18979-55-0 ]
[ 148731-15-1 ]

Yield	Reaction Conditions	Operation in experiment
87%	With dmap; dicyclohexyl-carbodiimide In chloroform at 20℃;
	With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 3h;	1.1 4-(benzyloxy)benzoic acid (20.0 g, 87.6 mmol), 4-(hexyloxy)phenol (17.0 g, 87.6 mmol), N,N'-dicyclohexylcarbodiimide (21.7 g, 105 mmol) and 4-dimethylaminopyridine (535 mg, 4.38 mmol) were dissolved in 300 mL of methylene chloride. The resulting solution was stirred for 3 hours at room temperature. Then, 300 mL of pure water was added thereto, and then the resulting liquid was filtered to remove insoluble matters. Thereafter, the obtained solution was subjected to separation operation, and the resulting methylene chloride solution was washed with a saturated aqueous sodium chloride solution and dried over magnesium sulfate. After methylene chloride was distilled off, the resulting solid matter was washed with methanol. Thereby, a white solid compound, 4-(hexyloxy)phenyl 4-(benzyloxy)benzoate (24.9 g) was obtained.

Reference： [1]Shreenivasa Murthy; Sadashiva [Journal of Materials Chemistry, 2005, vol. 15, # 20, p. 2056 - 2064]
[2]Current Patent Assignee: FUJIFILM HOLDINGS CORP. - US2012/238774, 2012, A1 Location in patent: Page/Page column 31-32

15
[ 836-43-1 ]
[ 1486-51-7 ]

Yield	Reaction Conditions	Operation in experiment
99.8%	With silica-supported Jones reagent In dichloromethane for 0.035h;
91%	With potassium hydroxide; zinc(II) oxide In 1,3,5-trimethyl-benzene at 164℃; for 18h; Inert atmosphere; Schlenk technique;
89%	With potassium hydroxide In water at 110℃; for 24h; Autoclave;	S5. Procedure for the synthesis of carboxylic acids General procedure: A magnetic stir bar and the alcohol were transferred to 8 mL glass vial and 2 mL of H2O was added. Then, 35mg catalyst was added followed by the addition of 50 mol% of KOH. The vial was f itted with a septum, cap,and needle. The reaction vials were placed into a 300 mL autoclave (8 vials containing different substrateswere placed at a time in the autoclave) and the autoclave was pressurized with 10 bar air. The autoclave wasplaced into an aluminium block and the temperature of the aluminium block was set in order obtain 110 °Cinside the autoclave. Temperature of the aluminium block was set to 120 oC to attain 110 oC inside theautoclave, which is considered as the reaction temperature. The reactions were allowed to progress undercontinuous stirring for the required time at 110 °C. After completion of the reaction, the autoclave was cooleddown to room temperature and the remaining air was gradually discharged. Af terwards, the catalyst wasf iltered-off and washed with water. The crude mixture was diluted with ethyl acetate. Then aqueous layer wasacidified with aq. HCl and the formed solid was f iltered. The solid was washed with diethyl ether twice anddried under vacuum. All products were analyzed by GC-MS and NMR spectroscopy analysis.

71%	With manganese(II) bromide; silver carbonate; potassium hydroxide In 1,3,5-trimethyl-benzene at 50 - 165℃; for 8h; Schlenk technique; Inert atmosphere;
70%	With sodium bromate; sodium hydrogen sulfate In acetonitrile for 35h; Heating;

Reference： [1]Wiles, Charlotte; Watts, Paul; Haswell, Stephen J. [Tetrahedron Letters, 2006, vol. 47, # 30, p. 5261 - 5264]
[2]Monda, Fabrizio; Madsen, Robert [Chemistry - A European Journal, 2018, vol. 24, # 67, p. 17832 - 17837]
[3]Bartling, Stephan; Beller, Matthias; Chandrashekhar, Vishwas G.; Jagadeesh, Rajenahally V.; Rabeah, Jabor; Rockstroh, Nils; Senthamarai, Thirusangumurugan [Chem, 2022, vol. 8, # 2, p. 508 - 531]
[4]Ghalehshahi, Hajar Golshadi; Madsen, Robert [Chemistry - A European Journal, 2017, vol. 23, # 49, p. 11920 - 11926]
[5]Shirini, Farhad; Zolfigol, Mohammad Ali; Torabi, Shayesteh [Synthetic Communications, 2006, vol. 36, # 19, p. 2833 - 2840]

16
[ 1486-51-7 ]
[ 460747-44-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 99 percent / oxalyl chloride; DMF / CH₂Cl₂ / 2 h / 23 °C 2: 95 percent / Et₃N / CH₂Cl₂ / 16 h / 25 °C 3: 83 percent / H₂ / Pd/C / methanol / 3464.89 Torr
	Multi-step reaction with 3 steps 1: (COCl)2; DMF / CH₂Cl₂ 2: Et₃N / CH₂Cl₂ 3: H₂ / Pd/C / methanol

Reference： [1]Cowart, Marlon; Faghih, Ramin; Curtis, Michael P.; Gfesser, Gregory A.; Bennani, Youssef L.; Black, Lawrence A.; Pan, Liping; Marsh, Kennan C.; Sullivan, James P.; Esbenshade, Timothy A.; Fox, Gerard B.; Hancock, Arthur A. [Journal of Medicinal Chemistry, 2005, vol. 48, # 1, p. 38 - 55]
[2]Faghih, Ramin; Dwight, Wesley; Gentles, Robert; Phelan, Kathleen; Esbenshade, Timothy A; Ireland, Lynne; Miller, Thomas R; Kang, Chae-Hee; Fox, Gerard B; Gopalakrishnan, Sujatha M; Hancock, Arthur A; Bennani, Youssef L [Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 15, p. 2031 - 2034]

17
[ 94-13-3 ]
[ 1486-51-7 ]

Reference： [1]Journal of Materials Chemistry,2001,vol. 11,p. 1332 - 1338

18
[ 1486-51-7 ]
[ 56442-43-4 ]

Yield	Reaction Conditions	Operation in experiment
94%	Stage #1: p-(benzyloxy)benzoic acid With oxalyl dichloride; N,N-dimethyl-formamide In tetrahydrofuran at 0 - 20℃; Stage #2: With ammonia In tetrahydrofuran; water at 0℃;	18.i Example 18; 2- {1- [2- (4- {2- [ (E)-2- (4-Chloro-2-fluoro-phenyl)-vinyl]-oxazol-4-ylmethoxy}- phenyl)-oxazol-4-yLrnethyl]-lH-imidazol-2-yl}-ethanol; i) 4-Benzyloxybenzamide; To a suspension of 4.565 g (20 mmol) 4-benzyloxybenzoic acid in 25 ml THF and 0.3 ml N, N-dimethylformamide was added dropwise at 0°C a solution of 2.6 ml oxalyl chloride in 5 ml THF. Stirring was continued for 3 hours at room temperature, then the suspension was added slowly to a stirred ice-cold solution of concentrated aqueous ammonia. The organic solvent was evaporated, 100 ml water added and the precipitate isolated and dried in vacuo at 50 °C. Yield: 4.29 g (94%) white solid. MS: M = 228.0 (API+) H~NMR (400MHzs D6-DMSO) : o= 5.16 (s, 2H, OCH2), 7.05 (d, 2H, Ar-H), 7.18 (br, 1H, NH), 7.38 (m, 3H, Ar-H), 7.46 (d, 2H, Ar-H), 7.85 (m, 3H, 2Ar-H + NH).
	Stage #1: p-(benzyloxy)benzoic acid With oxalyl dichloride Stage #2: With ammonia; water

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2005/40158, 2005, A1 Location in patent: Page/Page column 46
[2]Location in patent: body text Fu, Liqiang; Liu, Xin; Cheng, Jianjun; He, Huili; Cai, Zhan; Guo, Xingsheng; Ding, Shi; Yang, Yushe [Organic Process Research and Development, 2010, vol. 14, # 4, p. 815 - 819]

19
[ 18364-47-1 ]
[ 1486-51-7 ]
4-hydroxy-N-pyridin-3-yl-N-methyl-benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With HOAt; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In DMF (N,N-dimethyl-formamide); water; at 20℃; for 3h;	TO a solution of DMF/H20 (20MU7ML) is added 4-BENZYLOXY-BENZOIC acid (1G), 3-methyl-amino pyridine (710MG), HOAT (715mg), WSCD HCI (1G). The mixture is stirred for 3h at rt, diluted with ice water. The white precipitate is collected by filtration. To a solution of the above product in methanol is added PD/C, and the mixture is stirred for 12 h under H2 atmospheres. The reaction mixture is filtrated through-a pad of Celite and concentrated to give the title compound.

Reference： [1]Patent: WO2004/69256,2004,A1 .Location in patent: Page/Page column 30-31

20
[ 870-46-2 ]
[ 1486-51-7 ]
[ 860298-66-4 ]

Yield	Reaction Conditions	Operation in experiment
85%	With benzotriazol-1-ol; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride; triethylamine In DMF (N,N-dimethyl-formamide) at 20℃; for 48h;	11.a a) tert-butvl 2-f4- (benzyloxy) benzoyllhydrazinecarboxy ate A mixture of 4-benzyloxybenzoic acid (0.780 g, 3.42 mmol), tert-butyl carbazate (0. 443 g, 3.35 mmol), Et3N (0.5 mL), 1- (3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.05 g, 5.47 mmol) and 1-hydroxybenzotriazole hydrate (0.778 g, 5.76 mmol) in N, N-dimethylformamide (27 mL) was stirred at room temperature for 2 days. The reaction was concentrated and diluted in dichloromethane. The organic phase was washed twice with water, dried with MgS04 and concentrated. The residue was purified on column chromatography (silica gel, 5% MeOH in CH2C12) and tert-butyl 2- [4-(benzyloxy) benzoyl] hydrazine carboxylate (0.998 g, yield : 85 %) was identified by NMR spectroscopy. 'H-NMR (CDCb) : 8.21 (s, 1H), 7.76 (d, 2H), 7.37 (m, 5H), 6.95 (d, 2H), 6.76 (s, 1H), 5. 08 (s, 2H), 1. 48 (s, 9H).
	With N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride In dichloromethane at 20℃;

Reference： [1]Current Patent Assignee: MEDIVIR AB - WO2005/66131, 2005, A1 Location in patent: Page/Page column 38-39
[2]Gao, Ya-Ru; Guo, Rui-Li; Jia, Qiong; Wang, Meng-Yue; Wang, Yong-Qiang; Zhang, Hong-Xia; Zhang, Xing-Long; Zhao, Bao-Yin [Journal of Organic Chemistry, 2022]

21
[ 4319-49-7 ]
[ 1486-51-7 ]
[ 860298-84-6 ]

Yield	Reaction Conditions	Operation in experiment
90%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In DMF (N,N-dimethyl-formamide) at 20℃; for 2h;	49.a Example 49 4-[[6-[[[[(1S, 1aS, 7bS)-4,7-difluoro-1, 1a, 2, 7b-tetrahydrocyclopropa[c] [1] benzopyran- 1-vllaminolcarbonVllaminol-3-pvridinylloxyl-N-(4-morpholinVl)-benzamide a) N- (4-morpholinyl)-4- (phenylmethoxy)-benzamide A mixture of 4-benzyloxybenzoic acid (0.5 g, 2.19 mmol), 4-aminomorpholine (0.2 mL, 2.13 mmol), Et3N (0.316 mL), 1- (3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.671 g, 3.5 mmol) and 1-hydroxybenzotriazole hydrate (0.5 g, 3.7 mmol) in N, N-dimethylformamide (17 mL) was stirred at room temperature for 2 days. The reaction was concentrated and diluted in dichloromethane. The organic phase was washed twice with water, dried with MgS04 and concentrated. The residue was purified on column chromatography (silica gel, 5% MeOH in CH2CI2) and N- (4- morpholinyl)-4- (phenylmethoxy)-benzamide (0.615 g, yield : 90 %) was identified by NMR spectroscopy. 'H-NMR (CD30D): 7.99 (s, 1H), 7.78 (d, J = 8.6 Hz, 2H), 7.45 (m, 2H), 7.39 (m, 2H), 7.33 (m, 1H), 7.07 (d, J = 8.6Hz, 2H), 5.16 (s, 2H), 3.82 (m, 4H), 2.91 (m, 4H).

Reference： [1]Current Patent Assignee: MEDIVIR AB - WO2005/66131, 2005, A1 Location in patent: Page/Page column 101-102

22
[ 1486-51-7 ]
[ 3196-73-4 ]
[ 871250-21-4 ]

Yield	Reaction Conditions	Operation in experiment
92%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 12h;	2.A Preparation 2; 3- (4-Hydroxy-benzoylamino)-propionic acid methyl ester; Step A. 3- (4-Benzyloxy-benzoylamino)-propionic methyl ester; To a mixture of 4-benzyloxybenzoic acid (8.92 g, 39.08 mmol) and 3-amino- propionic acid methyl ester hydrochloride (6.00 g, 42.98 mmol) in CH2C12 (100 mL) was added DMAP (catalytic), triethylamine (6.60 mL, 47.35 mmol), and EDCI (9.00 g, 46.94 mmol). The mixture was stirred at RT for 12 h. The mixture was diluted with CH2C12. The organics were washed with IN HCI, 2N NaOH, water, and brine (1 x 100 mL each), and dried with MgS04 to yield 11.28 g (92%) of the title compound.

Reference： [1]Current Patent Assignee: ELI LILLY & CO - WO2005/118542, 2005, A1 Location in patent: Page/Page column 40

23
[ 1486-51-7 ]
[ 51207-66-0 ]
(4-benzyloxy-phenyl)-(2-(S)-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
34%	With N-cyclohexyl-carbodiimide-N'-propyloxymethyl polystyrene In DMF (N,N-dimethyl-formamide); dichloromethane at 20℃; for 72h;	1 To a suspension of 4-benzyloxybenzoic acid (116 mg, 0.51mmol) and PS- carbodiimide (500 mg, 0.66mmol, 1.32 mmol/g) in 5% DMF in CH2C12 (5 mL) is added (S) (+)-1-(2-pyrrolidinylmethyl)pyrrolidine (80 mg, 0.51 mmol). The mixture is stirred at room temperature for 3 days. The reaction mixture is filtered, and the resin is washed with CH2Cl2. The filtrate is concentrated and applied to silica-gel column chromatography (in CH2Cl2 followed by 5% 2M NH3 in MeOH / CH2Cl2) to give the product. 62.7 mg (34%) : Observed mass: 365 (M+1).

Reference： [1]Current Patent Assignee: ELI LILLY & CO - WO2005/121080, 2005, A1 Location in patent: Page/Page column 27

24
[ 580-15-4 ]
[ 1486-51-7 ]
[ 849805-94-3 ]

Yield	Reaction Conditions	Operation in experiment
18%	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine In dichloromethane at 20℃;	Z+-3 To a solution of 6-aminoquinoline (500mg, 3.47mmol) and 4-benzyloxybenzoic acid (792mg, 3.47mmol) in dichloromethane (25mL) were added benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (1.84g, 4.16mmol) and triethylamine (0.58mL, 4.16mmol), and the solution was stirred overnight at room temperature. The solvent was evaporated, the residue was purified by NH silica gel column chromatography (hexane : ethyl acetate), and the title compound (218mg, 18%) was obtained as a white solid. 1H-NMR Spectrum (CDCl3) δ(ppm) : 5.16(2H, s), 7.08-7.10(2H, m), 7.36-7.47(6H, m), 7.65-7.68(1H, m), 7.89-7.91(2H, m), 7.97(1H, brs), 8.08-8.10(1H, m), 8.15-8.17(1H, m), 8.49-8.50(1 H, m), 8.84-8.86(1H, m).

Reference： [1]Current Patent Assignee: EISAI CO LTD - EP1669348, 2006, A1 Location in patent: Page/Page column 76

25
[ 402860-21-3 ]
[ 1486-51-7 ]
[ 402860-22-4 ]

Yield	Reaction Conditions	Operation in experiment
84%	In ethanol ethyl acetate	4-Hydroxy-benzoic acid (R)1-methyl-6-(1,1,3,3,3-pentamethyl-disiloxanyl)hexyl ester (35) 4-Hydroxy-benzoic acid (R)1-methyl-6-(1,1,3,3,3-pentamethyl-disiloxanyl)hexyl ester (35) A solution of 4-benzyloxy-benzoic acid (Rs 1-methyl-6-(1,1,3,3,3-pentamethyl-disiloxanyl)-hexyl ester (34) (1 equi.) and palladium-carbon (10%) (0.01 equi.) in ethyl acetate-ethanol (4:1) (25 mL/mmole) was degassed under vacuum and the reaction mixture was stirred at room temperature under constant flow of hydrogen gas for 14 h. The reaction mixture passed through 2" celite-silica gel plug to remove Pd-C catalyst, concentrated in vacuo and recrystallized from acetonitrile-ethanol (3:1) to give 4-hydroxy-benzoic acid (R)-1-methyl-6-(1,1,3,3,3-pentamethyl-disiloxanyl) hexyl ester (35) as a colorless oil (84%).

Reference： [1]Current Patent Assignee: CITIZEN WATCH CO LTD - US2003/17278, 2003, A1

26
[ 79-37-8 ]
[ 1486-51-7 ]
[ 1486-50-6 ]

Yield	Reaction Conditions	Operation in experiment
85%	In 1,4-dioxane; <i>N</i>-methyl-acetamide	A.2 Intermediate B 2. 4-(Phenylmethoxy)benzoyl chloride. 4-(Phenylmethoxy)benzoic acid (500 mg, 2.2 mmol) was stirred with oxalyl chloride (280 mg, 2.2 mmol) and dimethylformamide (25 mg) in 1,4-dioxan (25 mL) for 20 min. The solvent and catalyst were evaporated under reduced pressure. The residue was recrystallized from hexanes to give 4-(phenylmethoxy)benzoyl chloride (460 mg, 85%).
112%	In dichloromethane	71.A 4-(benzyloxy)benzoyl Chloride Example 71A 4-(benzyloxy)benzoyl Chloride 4-Benzyloxybenzoic acid (15.0 g, 65.72 mmol) in dichloromethane (150 mL) and dimethylformamide (0.75 mL) was cooled to 0° C. After 30 minutes, the mixture was treated with neat oxalyl chloride (11.5 mL, 131.44 mmol) dropwise over 25 minutes. The resulting mixture was stirred at room temperature for 120 minutes followed by evaporation of solvent under reduced pressure to provide the title compound as a light yellow solid (18.2 g, 112% yield). 1H-NMR (300 MHz, CDCl3) δ 7.03 (d, 2H, J=8.9 Hz), 7.23-7.43 (m, 5H), 8.07 (d, 2H, J=8.9 Hz).
112%	In dichloromethane	71.A 4-(benzyloxy)benzoyl chloride EXAMPLE 71A 4-(benzyloxy)benzoyl chloride 4-Benzyloxybenzoic acid (15.0 g, 65.72 mmol) in dichloromethane (150 mL) and dimethylformamide (0.75 mL) was cooled to 0° C. After 30 minutes, the mixture was treated with neat oxalyl chloride (11.5 mL, 131.44 mmol) dropwise over 25 minutes. The resulting mixture was stirred at room temperature for 120 minutes followed by evaporation of solvent under reduced pressure to provide the title compound as a light yellow solid (18.2 g, 112% yield). 1H-NMR (300 MHz, CDCl3) δ7.03 (d, 2H, J=8.9 Hz), 7.23-7.43 (m, 5H), 8.07 (d, 2H, J=8.9 Hz).

	In dichloromethane	1 Preparation of 4-Benzyloxybenzoyl chloride EXAMPLE 1 Preparation of 4-Benzyloxybenzoyl chloride To a flask equipped with a magnetic stirrer and drying tube was added 4-benzyloxybenzoic acid (30.0 grams), anhydrous dichloromethane (200 mL), and then oxalyl chloride (28.7 mL). The resulting mixture was stirred at room temperature for 16 hours and the solvent removed in vacuo to yield 43.2 grams of the desired acid chloride as a white solid.
	In dichloromethane	8 Preparation of 4-Benzyloxybenzoyl Chloride Example 8 Preparation of 4-Benzyloxybenzoyl Chloride To a flash equipped with a magnetic stirrer and drying tube was added 75.0 grams of 4-benzyloxybenzoic acid and 700 mL of anhydrous methylene chloride and then 72 mL of oxalyl chloride. The resulting mixture was stirred at room temperature for 16 hours and then the solvent was removed in vacuo to yield 79.6 grams of the desired acid chloride.
	In dichloromethane	1 Preparation of 4-Benzyloxybenzoyl chloride Example 1 Preparation of 4-Benzyloxybenzoyl chloride To a flask equipped with a magnetic stirrer and drying tube was added 4-benzyloxybenzoic acid (30.0 grams), anhydrous dichloromethane (200 mL), and then oxalyl chloride (28.7 mL). The resulting mixture was stirred at room temperature for 16 hours and the solvent removed in vacuo to yield 43.2 grams of the desired acid chloride as a white solid.
	In tetrahydrofuran; benzene	1 EXAMPLE 1 Next, 11.4 g of this 4-benzyloxybenzoic acid was charged in a flask of 200 ml volume equipped with a calcium chloride tube and 50 ml each of dry THF and dry benzene were added. In addition, 10.0 g of oxalyl chloride was added to the mixture followed by reacting at room temperature for 12 hours with stirring. After the reaction, THF, benzene, the unreacted oxalyl chloride and the gas generated were removed under reduced pressure to give 12.0 g of 4-benzyloxybenzoyl chloride.
	In dichloromethane	4 Preparation of 4-Benzyloxybenzoyl chloride Example 4 Preparation of 4-Benzyloxybenzoyl chloride To a flask equipped with a magnetic stirrer and drying tube was added 4-benzyloxybenzoic acid (30.0 grams), anhydrous dichloromethane (200 mL), and then oxalyl chloride (28.7 mL). The resulting mixture was stirred at room temperature for 16 hours and the solvent removed in vacuoto yield 43.2 grams of the desired acid chloride as a white solid.
	In dichloromethane	1 Preparation of 4-Benzyloxybenzoyl chloride Example 1 Preparation of 4-Benzyloxybenzoyl chloride To a flask equipped with a magnetic stirrer and drying tube was added 4-benzyloxybenzoic acid (30.0 grams), anhydrous dichloromethane (200 mL), and then oxalyl chloride (28.7 mL). The resulting mixture was stirred at room temperature for 16 hours and the solvent removed in vacuoto yield 43.2 grams of the desired acid chloride as a white solid.
	In dichloromethane	2 Preparation of 4-Benzyloxybenzoyl Chloride Example 2 Preparation of 4-Benzyloxybenzoyl Chloride To a flask equipped with a magnetic stirrer and drying tube was added 75.0 grams of 4-benzyloxybenzoic acid and 700 mL of anhydrous methylene chloride and then 72 mL of oxalyl chloride. The resulting mixture was stirred at room temperature for 16 hours and then the solvent was removed in vacuoto yield 79.6 grams of the desired acid chloride.
	In diethyl ether	1 Preparation of 4-Benzyloxybenzoyl Chloride Example 1 Preparation of 4-Benzyloxybenzoyl Chloride To a flask equipped with a magnetic stirrer and drying tube was added 10.0 grams of 4-benzyloxybenzoic acid and 100 mL of anhydrous diethyl ether and then 19.1 mL of oxalyl chloride. The resulting mixture was stirred at room temperature for 16 hours and then the solvent was removed in vacuo to yield 10.8 grams of the desired acid chloride.
	In diethyl ether	1 Preparation of 4-Benzyloxybenzoyl Chloride Example 1 Preparation of 4-Benzyloxybenzoyl Chloride To a flask equipped with a magnetic stirrer and drying tube was added 10.0 grams of 4-benzyloxybenzoic acid and 100 mL of anhydrous diethyl ether and then 19.1 mL of oxalyl chloride. The resulting mixture was stirred at room temperature for 16 hours and then the solvent was removedin vacuo to yield 10.8 grams of the desired acid chloride.

Reference： [1]Current Patent Assignee: GENERAL ELECTRIC CO; BAYER AG - US5618528, 1997, A
[2]Current Patent Assignee: ABBVIE INC - US2002/169188, 2002, A1
[3]Current Patent Assignee: ABBOTT LABORATORIES INC - US2002/183309, 2002, A1
[4]Current Patent Assignee: CHEVRON CORP - US5466268, 1995, A
[5]Current Patent Assignee: CHEVRON CORP - US5713966, 1998, A
[6]Current Patent Assignee: CHEVRON CORP - US5786499, 1998, A
[7]Current Patent Assignee: TAKI CHEMICAL CO., LTD. - US4908373, 1990, A
[8]Current Patent Assignee: CHEVRON CORP - EP719762, 1996, A2
[9]Current Patent Assignee: CHEVRON CORP - EP752415, 1997, A1
[10]Current Patent Assignee: CHEVRON CORP - EP782980, 1997, A1
[11]Current Patent Assignee: CHEVRON CORP - EP636164, 2000, B1
[12]Current Patent Assignee: CHEVRON CORP - EP687288, 2001, B1

27
[ 1486-51-7 ]
[ 6276-54-6 ]
[ 530-62-1 ]
[ 222422-41-5 ]

Yield	Reaction Conditions	Operation in experiment
85%	With sodium carbonate In water; N,N-dimethyl-formamide	87 4-Benzyloxy-N-(3-chloro-propyl)-benzamide EXAMPLE 87 4-Benzyloxy-N-(3-chloro-propyl)-benzamide A mixture of 4-benzyloxy benzoic acid (5.0 g, 21.9 mmol), 1,1,-carbonyl-diimidazole (3.6 g, 1.05 eq.) and DMF (50 ml) was stirred at 50° C. for 1 h. After cooling to r.t., 3-chloropropylamine hydrochloride (3.4 g, 26.1 mmol) and sodium carbonate (3.5 g, 32.0 mmol) were added and stirring continued for 45 min. After the addition of water, the mixture was extracted with ether. The organic layer was dried (Na2 SO4), filtered and evaporated to give 4-benzyloxy-N-(3-chloro-propyl)-benzamide (5.44 g, 85%) as a white solid. MS: me/e=304 (M+H)+.

Reference： [1]Current Patent Assignee: EVOTEC AG - US5889026, 1999, A

28
aqueous sulphuric acid [ No CAS ]
[ 56442-22-9 ]
[ 1486-51-7 ]

Yield	Reaction Conditions	Operation in experiment
80%	With sodium hydroxide In ethanol; water	A.1 Intermediate B Phenylmethyl 4-(phenylmethoxy)benzoate (48.8 g, 150 mmol) was boiled under reflux with aqueous sodium hydroxide (2M; 250 mL) and ethanol (250 mL) for 4 h. The ethanol was evaporated under reduced pressure. Water (1000 mL) was added. The white solid was collected by filtration, warmed to 65° C. with aqueous sulphuric acid (2M; 300 mL) for 1 h and extracted with warm ethyl acetate. The ethyl acetate solution was dried with anhydrous magnesium sulphate and the solvent was evaporated under reduced pressure to give 4-(phenylmethoxy)benzoic acid (27.15 g, 80%).

Reference： [1]Current Patent Assignee: GENERAL ELECTRIC CO; BAYER AG - US5618528, 1997, A

29
petroleum [ No CAS ]
[ 6169-06-8 ]
[ 1486-51-7 ]
petrol [ No CAS ]
[ 111153-20-9 ]

Yield	Reaction Conditions	Operation in experiment
85.3%	With thionyl chloride; In pyridine; dichloromethane; toluene;	Step B(i) S(+)-1-Methylheptyl 4-benzyloxybenzoate 4-Benzyloxybenzoic acid (55 g) was converted to the acid chloride with thionyl chloride (120 ml) as described in example 1, and then reacted with S(+)-2-octanol (31.4 g) in pyridine (150 ml) and toluene (250 ml). The crude, yellow liquid product (80.7 g) was adsorbed on a mixture of alumina (240 g) and silica gel (240 g) from petroleum spirit (60-80) and eluted with a 1:1 mixture of petrol and dichloromethane. The product was obtained as a colourless oil (70.0 g, 85.3% yield).

Reference： [1]Patent: US5061399,1991,A

30
[ 1806-26-4 ]
[ 1486-51-7 ]
[ 102413-75-2 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; thionyl chloride; sodium chloride	3.S Synthesis of 4'-n-octylphenyl 4-benzyloxybenzoate First Stage Synthesis of 4'-n-octylphenyl 4-benzyloxybenzoate A 100-ml flask was charged with 8.2 g of 4-benzyloxybenzoic acid and 50 ml of thionyl chloride, and reaction was carried out under reflux for 2.5 hours. Excessive thionyl chloride was distilled under reduced pressure to obtain a crude crystal. Recrystallization gave 7.9 g of an acid chloride. EQU3 To a mixture of 35 ml of dry pyridine and 5.01 g of 4-n-octylphenol was added 6 g of the acid chloride under ice cooling. The temperature was gradually elevated to room temperature and reaction was carried out at 50° C. for 2 hours. After completion of the reaction, the precipitate was recovered by filtration and extracted with ethyl acetate. The organic layer was washed with water, 2N HCl, water, 5% NaOH, water and a saturated aqueous solution of sodium chloride in sequence and dried, and the organic solvent was distilled under reduced pressure. The obtained crude product was purified by column chromatography to obtain 8.13 g of an ester.

Reference： [1]Current Patent Assignee: TEIKOKU CHEMICAL INDUSTRIES CO., LTD.; SEIKO HOLDINGS CORPORATION - US4710585, 1987, A

31
[ 79-37-8 ]
[ 1486-50-6 ]
[ 2043-47-2 ]
[ 1486-51-7 ]
[ 252011-54-4 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In toluene;	Example 14 Production of Exemplified Compound 126 {circle around (1)}: A solvent comprising 1.1 g of triethylamine and 5 g of toluene was added dropwise to a mixture comprising 2.47 g of 4-benzyloxybenzoic chloride (this compound was prepared from 4-benzyloxybenzoic acid and oxalyl chloride), 2.64 g of 2-n-perfluorobutylethanol and 10 g of toluene in 30 minutes. After finishing the adding dropwise, the mixture was stirred at room temperature for 6 hours. Deposited salts were filtered off, and the filtrate was neutralized with 1/2 N hydrochloric acid and washed with water. Then, toluene was distilled off under reduced pressure, and the resultant residue was recrystallized from methanol, whereby 3.3 g of 4-benzyloxybenzoic acid 2'-n-perfluorobutylethyl ester was obtained in the form of a colorless crystal.

Reference： [1]Patent: US6217793,2001,B1

32
[ 1486-51-7 ]
[ 5735-53-5 ]
(4-benzyloxyphenyl)-(2,3-dihydrobenzo[1,4]oxazin-4-yl)-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In chloroform at 0 - 20℃;	88.1 Production of (2,3-dihydrobenzo[1,4]oxazin-4-yl)-(4-hydroxyphenyl)-methanone Step 1 Production of (4-benzyloxyphenyl)-(2,3-dihydrobenzo[1,4]oxazin-4-yl)-methanone 3,4-Dihydro-2H-benzo[1,4]oxazine (270 mg) obtained in Step 2 of Example 1, 4-benzyloxybenzoic acid (457 mg) and 4-dimethylaminopyridine (269 mg) were dissolved in chloroform (7 mL), and WSC.HCl (422 mg) was added under ice-cooling. After stirring overnight at room temperature, the reaction mixture was purified by silica gel chromatography (n-hexane-ethyl acetate=3:1) to give the title compound (636.2 mg) as an orange oil.
	With dmap In chloroform at 0 - 40℃;	88.1 Step 1 Production of (4-benzyloxyphenyl)-(2,3-dihydrobenzo[1,4]oxazin-4-yl)-methanone 3,4-Dihydro-2H-benzo[1,4]oxazine (270 mg) obtained in Step 2 of Example 1, 4-benzyloxybenzoic acid (457 mg) and 4-dimethylaminopyridine (269 mg) were dissolved in chloroform (7 mL), and WSC.HCl (422 mg) was added under ice-cooling. After stirring overnight at room temperature, the reaction mixture was purified by silica gel chromatography (n-hexane-ethyl acetate=3:1) to give the title compound (636.2 mg) as an orange oil.

Reference： [1]Current Patent Assignee: JAPAN TOBACCO INC - US2007/10670, 2007, A1 Location in patent: Page/Page column 103
[2]Current Patent Assignee: JAPAN TOBACCO INC - US2008/64871, 2008, A1 Location in patent: Page/Page column 66

33
[ 1486-51-7 ]
[ 6638-79-5 ]
[ 252199-28-3 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In 1,4-dioxane; acetonitrile at 20℃; for 24h;	1 Preparation 1 4-benzyloxy-N-methoxyl-N-methyl-benzamide To a solution of 4-Benzyloxy-benzoic acid (46.17 g) in dioxane (500 ml)/acetonitrile (500 ml) was added triethyl amine (38 ml) and O,N-Dimethyl-hydroxylamine hydrogen chloride (28 g) and the reaction mixture stirred at ambient temperature from 24 hours. The reaction mixture was filtered (triethyl amine hydrogen chloride) and concentrated. The reaction mixture was dissolved in methylene chloride and washed with water, dried magnesium sulfate, filtered and concentrated to provide the title compound (54 g). MS: (M+H m/z=272.3)
	With triethylamine; 1,1'-carbonyldiimidazole In dichloromethane at 20℃;

Reference： [1]Current Patent Assignee: PFIZER INC - US2007/155779, 2007, A1 Location in patent: Page/Page column 16
[2]Li, Junfeng; Jin, Hongjun; Zhou, Haiying; Rothfuss, Justin; Tu, Zhude [MedChemComm, 2013, vol. 4, # 2, p. 443 - 449]

34
[ 943755-41-7 ]
[ 1486-51-7 ]
N-[3-(2-amino-{1-[4-(benzyloxy)benzoyl]piperidin-4-yl}-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl)phenyl]-2-methoxyacetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃; for 14h;	33 EXAMPLE 33; Preparation of N-[3-(2-Amino-{1-]4-(benzyloxy)benzoyl]piperidin-4-yl}-1-methyl-5-oxo-4,5-dihydro-1H-imidazol-4-yl)phenyl]-2-methoxyacetamide; A cooled solution of N-[3-(2-amino-1-methyl-5-oxo-4-piperidin-4-yl-4,5-dihydro-1H imidazol-4-yl)phenyl]-2-methoxyacetamide (180 mg, 0.5 mmol) and p-benzyloxybenzoic acid (114 mg, 0.5 mmol) in methylene chloride and DMF is treated portionwise with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (105 mg, 0.55 mmol) at 0° C., stirred for 2 h at 0° C.and for 12 h at room temperature and concentrated in vacuo. The resultant residue is purified by flash chromatography (silica gel, EtOAc/2.0M ethanolic NH3: 80/20) to afford the title compound as a white solid, (80% yield), mp 149-152° C., MS (+) ES: 570 [M+H]+.

Reference： [1]Current Patent Assignee: PFIZER INC - US2007/191431, 2007, A1 Location in patent: Page/Page column 14

35
[ 1486-51-7 ]
[ 81863-45-8 ]
[ 1126369-46-7 ]

Yield	Reaction Conditions	Operation in experiment
96%	With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 0 - 80℃;	58.58a To a mixture of 4-(benzyloxy)benzoic acid (26 g, 113.91 mmol) and (3-amino-4- methylphenyl)methanol (15.63 g, 113.91 mmol), HATU (52.0 g, 136.70 mmol) in DMF (250 mL) was added DIPEA (39.8 mL, 227.83 mmol) at 00C. The mixture was stirred at 800C overnight. Water (~1L) was added to the mixture, and the solid precipitate was collected by filtration, washed with water, dried, then washed with Et2O (2 x), and dried to yield the title compound as a light yellow solid (38.0 g, 96 %). MS (M+H+) = 348.

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2009/27746, 2009, A1 Location in patent: Page/Page column 72

36
[ 1486-51-7 ]
[ 5373-87-5 ]
C₂₂H₂₀N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 6h;	EDC (246 mg, 1.27 mmol) in methylene chloride (5.0 mL) was added to a solution of 4-benzyloxybenzoic acid (279 mg, 1.21 mmol) and benzylhydroxyamidine (201 mg, 1.21 mmol) in methylene chloride (10.0 ml_). The mixture was stirred for 6 hours and checked by TLC for completion. Then tetrabutylammonium fluoride (1.0 M in THF, 2.42 mmol 2.3 ml_) was added dropwise and the solution was stirred at room temperature for 13 hours 30 minutes. The solid residue was purified by column chromatography over silica gel (EtOAc/Hex 1 :4 to 1 :2) and was crystallized from ethyl acetate to give a white crystaline material (74 mg 17%). 1H NMR (500 MHz, CDCL3) d(ppm): 3.88 (3H, s), 5.15 (2H, s), 7.01 (2H, d, J = 8.8 Hz), 7.10 (2H, d, J = 8.8 Hz),7.40-7.46 (4H, m), 8.10 (2H, d, J = 8.6 Hz), 8.15 (2H, d, J = 8.6 Hz). 13C NMR (125 MHz, CDCL3) d(ppm): 55.6 (CH3), 70.4 (CH2), 114.4 (CH), 115.5 (CH), 117.4, 119.8, 127.8 (CH), 128.5 (CH), 128.9 (CH), 129.3 (CH), 130.3 (CH), 136.3, 162.0, 162.4, 168.7, 175.5. MS (FAB+): 359 (MH+). HRMS fOr C22Hi8N2O3 (MH+): calculated: 359.1396; found 359.1392.

Reference： [1]Current Patent Assignee: THE UNIVERSITY OF NOTRE DAME DU LAC - WO2009/41972, 2009, A1 Location in patent: Page/Page column 24-25

37
[ 356084-02-1 ]
[ 1486-51-7 ]
[ 1136832-70-6 ]

Yield	Reaction Conditions	Operation in experiment
27%	Stage #1: (Z)-N′-hydroxy-4-phenoxybenzamidine; p-(benzyloxy)benzoic acid With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran; dichloromethane for 28h; Stage #2: With tetrabutyl ammonium fluoride In tetrahydrofuran; dichloromethane at 20℃; for 53.5h;	3.b To a solution of 4-benzyloxybenzoic acid (152 mg, 665 μmol) and benzylhydroxy-amidine (152 mg, 665 μmol) in methylene chloride (10.0 mL) was added EDC (135 mg, 698 7μmol) in methylene chloride (5.0 mL).The mixture was stirred for 5 hours. Then tetrabutylammonium fluoride (1.0 M in THF, 1.33 ml_) was added dropwise and the solution was stirred at room temperature for 28.5 hours. An additional (191 mg, 996 mmol) of EDC was added and the solution was stirred for 23 hours then an additional amount of tetrabutylammonium fluoride (1.0 M in THF, 1.33 ml_) was added and the solution was stirred for 25 hours. The product was purified by column chromatography EtOAc/Hex (1 :4 ? 1 :2) and was crystallized from ethylacetate/hexane (1 :1 ) to give a white crystalline material (75 mg, 27%). 1H NMR (500 MHz, CDCL3) d(ppm): 5.15 (2H, s), 7.07-7.12 (6H, m), 7.17 (1 H, t, J = 7.4 Hz) 7.34-7.46 (7H, m), 8.12 (2H, d, J = 9.0 Hz), 8.15 (2H, d, J = 8.4 Hz). 13C NMR (125 MHz, CDCL3) <5(ppm): 70.4 (CH2), 115.5 (CH), 117.3, 118.6 (CH), 119.9 (CH), 121.9, 124.3 (CH), 127.7 (CH), 128.5 (CH), 128.9 (CH), 129.4 (CH), 130.2 (CH), 130.3 (CH), 136.3, 156.4, 160.2, 162.5, 168.5, 175.6. MS (FAB+): 421 (MH+). HRMS for C27H20F3N2O3 (MH+): calculated: 421.1552; found 421.1540.
27%	Stage #1: (Z)-N′-hydroxy-4-phenoxybenzamidine; p-(benzyloxy)benzoic acid With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 5h; Stage #2: With tetrabutyl ammonium fluoride In tetrahydrofuran; dichloromethane at 20℃;	3.b To a solution of 4-benzyloxybenzoic acid (152 mg, 665 μmol) and benzylhydroxy-amidine (152 mg, 665 μmol) in methylene chloride (10.0 mL) was added EDC (135 mg, 698 μmol) in methylene chloride (5.0 mL). The mixture was stirred for 5 hours. Then tetrabutylammonium fluoride (1.0 M in THF, 1.33 mL) was added dropwise and the solution was stirred at room temperature for 28.5 hours. An additional (191 mg, 996 mmol) of EDC was added and the solution was stirred for 23 hours then an additional amount of tetrabutylammonium fluoride (1.0 M in THF, 1.33 mL) was added and the solution was stirred for 25 hours. The product was purified by column chromatography EtOAc/Hex (1:4→1:2) and was crystallized from ethylacetate/hexane (1:1) to give a white crystalline material (75 mg, 27%). 1H NMR (500 MHz, CDCL3) δ(ppm): 5.15 (2H, s), 7.07-7.12 (6H, m), 7.17 (1H, t, J=7.4 Hz) 7.34-7.46 (7H, m), 8.12 (2H, d, J=9.0 Hz), 8.15 (2H, d, J=8.4 Hz). 13C NMR (125 MHz, CDCL3) δ(ppm): 70.4 (CH2), 115.5 (CH), 117.3, 118.6 (CH), 119.9 (CH), 121.9, 124.3 (CH), 127.7 (CH), 128.5 (CH), 128.9 (CH), 129.4 (CH), 130.2 (CH), 130.3 (CH), 136.3, 156.4, 160.2, 162.5, 168.5, 175.6. MS (FAB+): 421 (MH+). HRMS for C27H20F3N2O3 (MH+): calculated: 421.1552; found 421.1540.

Reference： [1]Current Patent Assignee: THE UNIVERSITY OF NOTRE DAME DU LAC - WO2009/41972, 2009, A1 Location in patent: Page/Page column 12-13; Sheet 2
[2]Current Patent Assignee: THE UNIVERSITY OF NOTRE DAME DU LAC - US2010/261673, 2010, A1 Location in patent: Page/Page column title page; 1; 5

38
[ 1486-51-7 ]
[ 17929-90-7 ]
[ 1004764-59-3 ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: p-(benzyloxy)benzoic acid With oxalyl dichloride In dichloromethane at 0 - 20℃; Stage #2: 3-aminoazepan-2-one With triethylamine In dichloromethane at 20℃; for 1h;	15.15.1 15.1 Synthesis of 4-(benzyloxy)-N-(2-oxoazepan-3-yl)benzamide a46. A suspension of 4-(benzyloxy)benzoic acid a45 (5.0 g, 21.93 mmol, 1 eq) andN,N-dimethylformamide (0.5 ml) in dichloromethane (300 ml) at 00C is treated with oxalyl chloride (2.83 ml, 26.32 mmol, 1.2 eq). The mixture is left to warm up to room temperature and stirred until gas evolution has ceased. Half of the solvent is removed under reduced pressure and the resulting solution is added to a mixture of DL-α- amino-ε-caprolactam (3.37 g, 26.32 mmol, 1.2 eq) and triethylamine (6.1 1 ml, 43.86 mmol, 2 eq) in dichloromethane (300 ml). After 1 h stirring at 200C, water (200 ml) is added and the organic layer is dried over magnesium sulfate and concentrated. The residue is taken up with ethyl acetate, the resulting suspension is filtered and the solid dried at 400C under reduced pressure to afford 5.9 g of 4-benzyloxy-N-(2-oxoazepan-3- yl)benzamide a46. Yield: 80 %. LC-MS (MH+): 339.
80%	Stage #1: p-(benzyloxy)benzoic acid With oxalyl dichloride In dichloromethane Stage #2: 3-aminoazepan-2-one With triethylamine In dichloromethane at 20℃; for 1h;

Reference： [1]Current Patent Assignee: UCB - WO2009/92764, 2009, A1 Location in patent: Page/Page column 79
[2]Location in patent: scheme or table Denonne, Frederic; Celanire, Sylvain; Christophe, Bernard; Defays, Sabine; Delaunoy, Christel; Delporte, Marie-Laure; Detrait, Eric; Durieu, Veronique; Gillard, Michel; Lamberty, Yves; Lorent, Genevieve; Nicolas, Jean-Marie; van Bellinghen, Alain; van Houtvin, Nathalie; Provins, Laurent [ChemMedChem, 2011, vol. 6, # 9, p. 1559 - 1565]

39
[ 6320-39-4 ]
[ 1486-51-7 ]
[ 1004764-42-4 ]

Yield	Reaction Conditions	Operation in experiment
71%		16.1 Synthesis of 4-(benzyloxy)-N-(4-hydroxypyridin-3-yl)benzamide a50.A suspension of 4-(benzyloxy)benzoic acid a45 (10.0 g, 43.81 mmol, 1 eq) and N,N-dimethylformamide (0.5 ml) in dichloromethane at 00C is treated with oxalyl chloride (5.18 ml, 48.19 mmol, 1.1 eq). The mixture is left to warm up to room temperature. When gas evolution has stopped, half of the solvent is removed under reduced pressure, and the solution is added dropwise to a solution of 3-aminopyridin-4- ol (4.82 g, 43.81 mmol, 1 eq) and triethylamine (12.15 ml, 87.62 mmol, 2 eq) in dichloromethane (300 ml). The mixture is stirred at 200C for 24 h and water (200 ml) is added. The aqueous phase is extracted with a 9:1 mixture of dichloromethane and methanol (2 x 300 ml). The combined organic layers are dried over magnesium sulfate and concentrated under reduced pressure. The residue is triturated with ethyl acetate (50 ml) and the resulting suspension is filtered off. The solid is dried at 400C in vacuo to yield 10 g of 4-(benzyloxy)-N-(4-hydroxypyridin-3-yl)benzamide a50.Yield: 71 %. LC-MS (MH+): 321.

Reference： [1]Patent: WO2009/92764,2009,A1 .Location in patent: Page/Page column 80

40
[ 623155-19-1 ]
[ 1486-51-7 ]
3-[4-(benzyloxy)benzoyl]amino}-N-cyclopropyl-4-methylbenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: p-(benzyloxy)benzoic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 2h; Stage #2: 3-amino-N-cyclopropyl-4-methylbenzamide With pyridine In dichloromethane at 0 - 20℃; for 2h;	1 Example 1; 3-{ [4-(benzyloxy) benzoyl] amino}-N-cyclopropyl-4-methylbenzamide To a solution of 4-benzyloxybenzoic acid (11.0 g, 48 mmol) in DCM (100 mL) at 0°C was added oxalyl chloride (8.4 mL, 96 mmol) followed by DMF (two drops). The resulting mixture was stirred at room temperature for 2 hours. The mixture was evaporated giving a white solid which was dissolved in DCM (50 mL). The resulting solution was added portionwise to a stirred solution of 3-amino-N-cyclopropyl-4-methylbenzamide (7.61 g, 40 mmol) and pyridine (7.76 mL, 96 mmol) in DCM (100 mL) at 0°C. The resulting mixture was stirred at room temperature for 2 hours. The solid was collected by filtration and washed three times with DCM to give the title compound as a white solid (13.9 g, 87%); NMR Spectrum: (DMSOd6) 0.60 (m, 4H), 2.25 (s, 3H), 2.84 (m, 1H), 5.20 (s, 2H), 7.14 (d, 2H), 7.39 (m, 6H), 7.63 (d, 1H), 7.79 (s, 1H), 7. 97 (d, 2H), 8.37 (s, 1H), 9.82 (s, 1H) ; Mass Spectrum: M+H+ 399.

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2005/61465, 2005, A1 Location in patent: Page/Page column 40

41
[ 1204331-29-2 ]
[ 1486-51-7 ]
[ 1393368-49-4 ]

Yield	Reaction Conditions	Operation in experiment
57%	Stage #1: p-(benzyloxy)benzoic acid With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide for 1.5h; Stage #2: N-[4-(1,2,3,6-tetrahydro-pyridin-4-yl)-3-trifluoromethyl-benzoyl]-N'-(carbobenzyloxy)-guanidine With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃;	65.A To a solution of 4-(benzyloxy)-benzoic acid (52 mg, 0.23 mmol) in NN- dimethylformamide (3.0 mL) is added di-imidazol-1-yl-methanone (37 mg, 0.23 mmol) and the mixture is stirred for 90 minutes. The product from Example 47 Step E (100 mg, 0.21 mmol) is then added followed by NN-diisopropylethylamine (0.13 mL, 0.73 mmol) and the reaction is stirred overnight at room temperature. The mixture is diluted with ethyl acetate, washed twice with water, once with brine, dried over Na2SO4, filtered, and the solvent is removed in vacuo. The crude material is purified via silica gel chromatography using a gradient elution of 0-60% ethyl acetate/hexane to afford the desired product (78 mg, 57%). LCMS: 657.60 (M+H+).

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - WO2010/5783, 2010, A1 Location in patent: Page/Page column 127

42
[ 1486-51-7 ]
azetidine hydrochloride [ No CAS ]
[ 1208536-47-3 ]

Yield	Reaction Conditions	Operation in experiment
79%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 20℃;	1.1 Azetidine hydrochloride (10.3 g, 110 mmol), N-(3-dimethylaminopropyl)-N'- ethylcarbodiimide hydrochloride (25.2 g, 131 mmol), 1 -hydroxybenzotriazole (20.1 g, 131 mmol), and triethylamine (33.6 ml, 241 mmol) were added to a N,N-dimethylformamide solution (500 ml) of l-(benzyloxy)benzoate (25 g, 110 mmol), and this mixture was stirred overnight at room temperature. Water was added to this reaction solution, this mixture was extracted with ethyl acetate twice, followed by washing the organic layer with water and a saturated saline solution, drying the organic layer with anhydrous sodium sulfate, and thereafter concentrating this solvent under reduced pressure. The obtained residue was crystallized from chloroform- diethyl ether to obtain l-[4-(benzyloxy)-benzoyl] azetidine (23.0 g, yield: 79%) as an ecru solid.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2010/24110, 2010, A1 Location in patent: Page/Page column 22

43
[ 1486-51-7 ]
[ 34781-86-7 ]
[ 1219925-76-4 ]

Yield	Reaction Conditions	Operation in experiment
95%	With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0 - 20℃;	Compound 34. Referring to the scheme above, a mixture of 4-aminoresorsinol hydrochloride (5.3 g. 33 mmol). 4-benzyloxybenzoic acid (5.0 g, 22 mmol), 1- hydroxybenzotriazole (5.9 g. 44 mmol). benzotriazole-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (23 g, 44 mmol) and N.N-diisopropylethylamine (19 mL. 110 mmol) in dimethylformamide (DMF) (50 mL) was stirred at O0C to room temperature overnight. After concentration to remove DMF. the reaction mixture was purified by silica gel chromatography (20% to 80%EtOAc/hexane. EtOAc and 30%MeOH/EtOAc) to give desired amide Compound 41 (or/and ester. 7.3 g, 95%).
	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0 - 20℃;	EXAMPLE 4 Synthesis of Compound 34Cl' OBn- >JOBn- V OHO ~O ?Compound 43 Compound 44 Compound 45Compound 46 Compound 34[0052] Compound 34. Referring to the scheme above, a mixture of 4-aminoresorsinol hydrochloride (5.3 g. 33 mmol). 4-benzyloxybenzoic acid (5.0 g, 22 mmol). 1- hydroxybenzotriazole (5.9 g. 44 mmol), benzotriazole-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (23 g. 44 mmol) and N.N-diisopropylethylamine (19 mL. 1 10 mmol) in dimethylformamide (DMF) (50 mL) was stirred at O0C to room temperature overnight. After concentration to remove DMF. the reaction mixture was purified by silica gel chromatography (20% to 80%EtOAc/hexane. EtOAc and 30%MeOH/EtOAc) to give desired amide Compound 41 (or/and ester. 7.3 g. 95%).

Reference： [1]Patent: WO2010/36905,2010,A1 .Location in patent: Page/Page column 38-39
[2]Patent: WO2010/36908,2010,A1 .Location in patent: Page/Page column 13-14

44
[ 1486-51-7 ]
[ 34781-86-7 ]
[ 1219925-77-5 ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 4 Synthesis of Compound 34Cl' OBn- >JOBn- V OHO ~O ?Compound 43 Compound 44 Compound 45Compound 46 Compound 34[0052] Compound 34. Referring to the scheme above, a mixture of 4-aminoresorsinol hydrochloride (5.3 g. 33 mmol). 4-benzyloxybenzoic acid (5.0 g, 22 mmol). 1- hydroxybenzotriazole (5.9 g. 44 mmol), benzotriazole-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (23 g. 44 mmol) and N.N-diisopropylethylamine (19 mL. 1 10 mmol) in dimethylformamide (DMF) (50 mL) was stirred at O0C to room temperature overnight. After concentration to remove DMF. the reaction mixture was purified by silica gel chromatography (20% to 80%EtOAc/hexane. EtOAc and 30%MeOH/EtOAc) to give desired amide Compound 41 (or/and ester. 7.3 g. 95%).[0053] A solution of Compound 41 (7.3 g. 22 mmol) in acetic acid (90 mL) was heated at 120 C for 3 hours. The reaction mixture was cooled to room temperature and concentrated. The residue was purified by silica gel chromatography (10% to 30% EtOAc/hexanes) to give the desired product Compound 42 (2.0 g. 29%) as light yellow solid. 1H NMR (400 MHz. CD3OD) delta 8.09 (d. J=9.1 Hz. 2H). 7.47-7.4 (m. 6H). 7.16 (d. J=9.1 Hz. 2H), 7.02 (d. J=2.4 Hz. IH). 7.02 (dd. J=2.4. 8.5 Hz. IH). 5.18 (s. 2H): MS (ES") m/z 316.4.

Reference： [1]Patent: WO2010/36908,2010,A1 .Location in patent: Page/Page column 13-14

45
[ 1486-51-7 ]
[ 142665-13-2 ]
[ 1243707-74-5 ]

Yield	Reaction Conditions	Operation in experiment
38%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In methanol; at 20 - 25℃; for 20h;	Step 1 : N-(6-Amino-2,4-dioxo-3-propyl-l,2,3,4-tetrahydro-pyrimidin-5-yl)-4- benzyloxy-benzamide A mixture of 4-benzyloxy-benzoic acid ( 7.44g, 0.033mol ), 5, 6-diamino-3 -propyl- IH- pyrimidine-2,4-dione (5.0g, 0.027mol), methanol (60ml), EDCI (10.0g, 0.052mol), were taken and stirred for 20 hours at 20-25 C. The reaction mixture was concentrated and water (50ml) was added to obtain solid precipitate. The compound was purified by column chromatography to obtain N-(6-Amino-2,4-dioxo-3-propyl- 1,2,3, 4-tetrahydro- pyrimidin-5-yl)-4-benzyloxy-benzamide as light yellow solid (4.Og, 38%).
38%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In methanol; at 20 - 25℃; for 20h;	Step 1: N-(6-Amino-2,4-dioxo-3-propyl-1,2,3,4-tetrahydro-pyrimidin-5-yl)-4-benzyloxy-benzamide A mixture of 4-benzyloxy-benzoic acid (7.44 g, 0.033 mol), <strong>[142665-13-2]5,6-diamino-3-propyl-1H-pyrimidine-2,4-dione</strong> (5.0 g, 0.027 mol), methanol (60 ml), EDCI (10.0 g, 0.052 mol), were taken and stirred for 20 hours at 20-25 C. The reaction mixture was concentrated and water (50 ml) was added to obtain solid precipitate. The compound was purified by column chromatography to obtain N-(6-Amino-2,4-dioxo-3-propyl-1,2,3,4-tetrahydro-pyrimidin-5-yl)-4-benzyloxy-benzamide as light yellow solid (4.0 g, 38%). 1HNMR (400 MHz, DMSO d6): delta 0.82-0.90 (m, 3H); 1.47-1.49 (m, 2H); 3.65 (t, J=6.8 Hz, 2H); 5.19 (s, 2H); 6.04 (s, 2H); 7.08 (d, J=8.4 Hz, 2H); 7.32-7.48 (m, 5H); 7.93 (d, J=8.4 Hz, 2H); 8.75 (s, 1H); 10.44 (s, 1H).

Reference： [1]Patent: WO2010/103547,2010,A2 .Location in patent: Page/Page column 71
[2]Patent: US2012/115864,2012,A1 .Location in patent: Page/Page column 29

46
[ 1486-51-7 ]
[ 5373-87-5 ]
[ 1136832-88-6 ]

Yield	Reaction Conditions	Operation in experiment
17%	Stage #1: p-(benzyloxy)benzoic acid; (Z)-N'-hydroxy-4-methoxybenzenecarboximidamide With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 6h; Stage #2: With tetrabutyl ammonium fluoride In tetrahydrofuran; dichloromethane at 20℃;	EDC (246 mg, 1.27 mmol) in methylene chloride (5.0 mL) was added to a solution of 4-benzyloxybenzoic acid (279 mg, 1.21 mmol) and benzylhydroxyamidine (201 mg, 1.21 mmol) in methylene chloride (10.0 mL). The mixture was stirred for 6 hours and checked by TLC for completion. Then tetrabutylammonium fluoride (1.0 M in THF, 2.42 mmol 2.3 mL) was added dropwise and the solution was stirred at room temperature for 13 hours 30 minutes. The solid residue was purified by column chromatography over silica gel (EtOAc/Hex 1:4 to 1:2) and was crystallized from ethyl acetate to give a white crystalline material (74 mg 17%). 1H NMR (500 MHz, CDCL3) δ(ppm): 3.88 (3H, s), 5.15 (2H, s), 7.01 (2H, d, J=8.8 Hz), 7.10 (2H, d, J=8.8 Hz), 7.40-7.46 (4H, m), 8.10 (2H, d, J=8.6 Hz), 8.15 (2H, d, J=8.6 Hz). 13C NMR (125 MHz, CDCL3) δ(ppm): 55.6 (CH3), 70.4 (CH2), 114.4 (CH), 115.5 (CH), 117.4, 119.8, 127.8 (CH), 128.5 (CH), 128.9 (CH), 129.3 (CH), 130.3 (CH), 136.3, 162.0, 162.4, 168.7, 175.5. MS (FAB+): 359 (MH+). HRMS for C22H18N2O3 (MH+): calculated: 359.1396; found 359.1392.

Reference： [1]Current Patent Assignee: THE UNIVERSITY OF NOTRE DAME DU LAC - US2010/261673, 2010, A1 Location in patent: Page/Page column 10

47
[ 1486-51-7 ]
[ 613-92-3 ]
[ 1136832-85-3 ]

Yield	Reaction Conditions	Operation in experiment
22%	Stage #1: p-(benzyloxy)benzoic acid; N-hydroxyl-benzamidine With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 6h; Stage #2: With tetrabutyl ammonium fluoride In tetrahydrofuran; dichloromethane at 20℃;	EDC (299 mg, 1.54 mmol) in CH2Cl2 (5.0 mL) was added to a solution of 4-benzyloxybenzoic acid (336, 1.47 mmol) and benzylhydroxyamidine (200 mg, 1.47 mmol) in CH2Cl2 (5.0 mL). The mixture was stirred for 6 hours and checked by TLC for completion. Then tetrabutylammonium fluoride (1.0 M in THF, 2.95 mL) was added dropwise and the solution was stirred at room temperature for 12 hours. The solvent was removed under reduced pressure and the product was purified by column chromatography over silica gel (EtOAc/Hex (:4→1:2) and was crystallized from hot ethyl acetate to give a white crystalline material (107 mg, 22%). 1H NMR (500 MHz, CDCL3) δ(ppm): 5.16 (2H, s), 7.11 (2H, d, J=8.8 Hz), 7.36-7.46 (5H, m), 7.49-7.51 (3H, m), 8.16 (4H, d, J=8.6 Hz). 13C NMR (125 MHz, CDCL3) δ(ppm): 70.4 (CH2), 115.5 (CH), 117.3, 127.3, 127.7 (CH), 127.8 (CH), 128.5 (CH), 128.9, 129.0 (CH), 130.3 (CH), 131.3, 136.2, 162.5, 169.0, 175.8. MS (FAB+): 329 (MH+). HRMS for C21H16N2O2 (MH+): calculated: 329.1290; found 329.1302.

Reference： [1]Current Patent Assignee: THE UNIVERSITY OF NOTRE DAME DU LAC - US2010/261673, 2010, A1 Location in patent: Page/Page column 9

48
[ 1486-51-7 ]
[(2R,3R,4S,5R,6R)-3,4,5-Tris-benzyloxy-6-((2R,3R,4S,5R,6R)-3,4,5-tris-benzyloxy-6-hydroxymethyl-tetrahydro-pyran-2-yloxy)-tetrahydro-pyran-2-yl]-methanol [ No CAS ]
[ 1260071-66-6 ]

Yield	Reaction Conditions	Operation in experiment
68%	With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0℃; for 2h;	Typical synthetic procedure Triphenylphosphine (300 mg, 1.14 mmol), 2,3-dimethoxybenzoic acid (186 mg, 1.02 mmol), and diisopropyl azodicarboxylate (226 μl, 1.14 mmol) were added to a stirred solution of 2,2',3,3',4,4'-hexabenzyl-α,α-D-trehalose (3, 300 mg, 0.34 mmol) in dry THF (10 mL) at 0 °C. After stirring for 2 h at the same temperature, the reaction mixture was diluted with ice water and extracted with EtOAc. The organic layer was dried over anhydrous MgSO4, filtered, and concentrated. The residue was purified by silica gel column chromatography (hexane/EtOAc, 15-3:1) to give 4e (305.6 mg, 74.2%) as a colorless oil.
68%	With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0℃; Inert atmosphere;	Preparation of intermediates 3a-m General procedure: Triphenylphosphine(300mg, 1.14mmol), 2-methoxybenzoic acid (155mg, 1.02mmol) and di-isopropyl azodicarboxylate (226 ml, 1.14mmol) were added to a stirred solution of 2 (300mg, 0.34mmol) in dry THF (10ml) at 0° C. After stirring for 2 h at the same temperature, the reaction mixture was diluted with ice water and extracted with EtOAc. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography (hexane/EtOAc, 15B3:1) to give 3a

Reference： [1]Location in patent: experimental part Jiang, Yong-Li; Tang, Long-Qian; Miyanaga, Satoshi; Igarashi, Yasuhiro; Saiki, Ikuo; Liu, Zhao-Peng [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 4, p. 1089 - 1091]
[2]Jiang, Yong-Li; Miyanaga, Satoshi; Han, Xiu-Zhen; Tang, Long-Qiang; Igarashi, Yasuhiro; Saiki, Ikuo; Liu, Zhao-Peng [Journal of Antibiotics, 2013, vol. 66, # 9, p. 531 - 537]

49
[ 1486-51-7 ]
2,2-dimethylchroman-3,7-diol [ No CAS ]
[ 1310328-53-0 ]

Yield	Reaction Conditions	Operation in experiment
15.9%	With dmap; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 20℃;	5.9. General method for synthesis of compounds (17, 25-27) General prodedure: A mixture of appropriate benzoic acid (1.2 equiv), 2-(1-Hydroxy-1-methyl-ethyl)-2,3-dihydro-benzofuran-6-ol 37 or 2,2-dimethyl-chroman-3,7-diol 39 (1 equiv), DCC (3 equiv) and 4-dimethylaminopyridine (DMAP) (0.2 equiv) in DMF was stirred overnight at room temperature. Then the reaction mixture was partitioned between ethyl acetate and water. The organic phase was washed with brine, dried (MgSO4 anh), and concentrated. The residue was purified by silica gel flash column chromatography.

Reference： [1]Location in patent: experimental part Xia, Yan; Jin, Yinglan; Kaur, Navneet; Choi, Yongseok; Lee, Kyeong [European Journal of Medicinal Chemistry, 2011, vol. 46, # 6, p. 2386 - 2396]

50
[ 35583-15-4 ]
[ 1486-51-7 ]
[ 1312339-82-4 ]

Yield	Reaction Conditions	Operation in experiment
70%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;	2.1.3. General procedure for the preparation of 4-9. General procedure: A100 ml flask was charged with the diol (500 mg, 3.04 mmol,1.0 equiv.), the acid (6.08 mmol, 2.0 equiv.), 4-(dimethylamino)-pyridine (594 mg, 4.86 mmol, 1.6 equiv.), 3-[3-(dimethylamino)-propyl]-1-ethylcarbodiimide hydrochloride (EDACHCl; 1.282 g,6.69 mmol, 2.2 equiv.) and dichloromethane (40 ml). Thesuspension was stirred at room temperature for 48 h. Afterthis time, TLC on silica gel (eluent: hexane/ethyl acetate = 7:3)indicated the complete consumption of the starting materials.The mixture was washed with water (2 50 ml), brine (1 50 ml), aqueous citric acid at pH = 2 (2 50 ml) and a saturatedNaHCO3 aqueous solution (1 50 ml). The organiclayer was dried over Na2SO4 and concentrated under reducedpressure. The crude was purified by column chromatographyon silica gel (eluent: hexane/ethyl acetate = 90:1080:2070:30, unless otherwise stated) to afford the product.
64%	With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 12h;	2.k Diol 12 (50 mg, 0.3 mmol), 4-benzyloxybenzoic acid (291 mg, 0.61 mmol), dicyclohexylcarbodiimide (263 mg, 0.61 mmol) and 4-dimethylaminopyridine (9 mg, 0.07 mmol) were dissolved in dry DCM and stirred at rt for 12 h. The DCM was removed and EtOAc was added and kept in the freezer for 12 h. The formed ppt was filtered off and the crude product was purified by column chromatography to give product as white solid, m.p. 134° C.,) (115 mg, 64% yield): 1H NMR (400 MHz, CDCl3) δ: 3.23-3.4 (m, 4H), 5.09 (2, 4H), 5.67 (t, 2H), 6.93 (d, 4H), 7.14-7.41 (m, 14H), 7.92 (d, 4H); 13C NMR (500 MHz, CDCl3) δ: 165.6, 162.5, 136.1, 132.5, 131.7, 129.1, 128.6, 128.2, 127.4, 126.4, 122.7, 114.4, 70.0, 69.9, 32.2; ESI MS m/z: 607 (M+Na).

Reference： [1]Chan, Tak-Hang; Fukumoto, Kozo; Nishioka, Takanori; Renzetti, Andrea; Rutherford, Ryan Noboru; Ura, Shinji [Acta Crystallographica Section C: Structural Chemistry, 2020, vol. 76, p. 1085 - 1095]
[2]Current Patent Assignee: WAYNE STATE UNIVERSITY; HONG KONG POLYTECHNIC UNIVERSITY; MCGILL UNIVERSITY - US2011/152210, 2011, A1 Location in patent: Page/Page column 17; 23

51
[ 6320-39-4 ]
[ 1486-51-7 ]
[ 1004764-43-5 ]

Yield	Reaction Conditions	Operation in experiment
	With trichloroacetonitrile; triphenylphosphine; In acetonitrile; at 0 - 80℃; for 16h;	2-(4-Benzyloxy-phenyl)-oxazolo[4,5-c] pyridine (25, Ra=Rb=H).To a cooled (0C) suspension of commercially available 4-hydroxy-3-amino-pyridine (14, 19.3g, 175mmol) in acetonitril (1500ml) was added 4-benzyloxy-benzoic acid (24, Ra=Rb=H, 40g, 175mmol), triphenylphosphine (142.5g, 543mmol, 3.1eq) and trichloroactomtril (54.5ml, 543mmol, 3.1eq). The reaction mixture was allowed to reach room temperature and the mixture was stirred for 16hrs at 80C. The mixture was concentrated in vacuo and the residues was dissolved in DCM and washed with 2N NaOH (3x). The combined water layers were extracted with DCM and the organic layers dried (NaaSCU) to give crude 25 (Ra=Rb=H) as oil which was used in the next step without further purification.

Reference： [1]Patent: WO2012/4373,2012,A1 .Location in patent: Page/Page column 48

52
[ 1486-51-7 ]
1-(2-tert-butylphenyl)piperazine dihydrochloride [ No CAS ]
[ 1252655-71-2 ]

Yield	Reaction Conditions	Operation in experiment
79%	Stage #1: p-(benzyloxy)benzoic acid With oxalyl dichloride In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: 1-(2-tert-butylphenyl)piperazine dihydrochloride With triethylamine In tetrahydrofuran at 20℃;	17 Example 17 1-[4-(Benzyloxy)phenyl]carbonyl}-4-(2-tert-butylphenyl)piperazine To a stirred solution of 4-(benzyloxy)benzoic acid (913 mg) and N,N-dimethylformamide (0.01 mL) in tetrahydrofuran (30 mL) was added oxalyl chloride (0.508 mL) at room temperature. After 1 h the reaction mixture was concentrated under reduced pressure to provide the residue and the residue was dissolved in tetrahydrofuran (30 mL). A mixture of 1-(2-tert-butylphenyl)piperazine dihydrochloride obtained in Reference Example 1 (1.0 g) and triethylamine (1.67 mL) was added to the solution and stirred at room temperature for over-night. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by flash column chromatography (NH-silica gel, ethyl acetate) to provide the title compound (1360 mg, 79%) as a solid. 1H NMR (300 MHz, CDCl3) δ 1.45 (s, 9H), 2.84-2.90 (m, 4H), 3.10-3.38 (m, 2H), 3.80-4.00 (m, 1H), 4.60-4.70 (m, 1H), 5.09 (s, 2H), 6.90-7.02 (m, 2H), 7.12-7.46 (m, 11H). Anal. Calc. for C22H32N2O2: C, 78.47; H, 7.53; N, 6.54. Found: C, 78.40; H, 7.67; N, 6.52.

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US2012/71489, 2012, A1 Location in patent: Page/Page column 68-69

53
[ 1486-51-7 ]
[ 100-83-4 ]
[ 1392309-76-0 ]

Yield	Reaction Conditions	Operation in experiment
88.2%	Stage #1: p-(benzyloxy)benzoic acid; meta-hydroxybenzaldehyde With dmap In chloroform for 0.166667h; Inert atmosphere; Stage #2: With dicyclohexyl-carbodiimide In chloroform at 20℃; for 12h; Inert atmosphere;
86.2%	Stage #1: p-(benzyloxy)benzoic acid; meta-hydroxybenzaldehyde With dmap In dichloromethane for 0.5h; Inert atmosphere; Stage #2: With dicyclohexyl-carbodiimide In dichloromethane for 24h; Inert atmosphere;	2-1 Preparation of 3-formylphenyl4-(benzyloxy)benzoate 8.02 g (78.8 mmol) of 3-hydroxybenzaldehyde,15.0 g (65.7 mmol) of 4- (benzyloxy) benzoic acid and 0.80 g (6.57 mmol) of 4-dimethylaminopyridine (DMAP) were dissolved in MC and stirred for 30 minutes under a nitrogen atmosphere. N, N'dicyclohexylcarbodiimide (DCC) (78.8 mmol) were added thereto, and the mixture was stirred under a nitrogen atmosphere for 24 hours. After the completion of the reaction, the urea produced was filtered off on filter paper, washed three times with aqueous NaCl solution and distilled water, and then subjected to vacuum distillation and column chromatography using a single solvent of dichloromethane as a developing solvent. The resulting solution was distilled under reduced pressure and vacuum dried to obtain a white solid product, 3-formylphenyl 4- (benzyloxy) benzoate.
84.2%	Stage #1: meta-hydroxybenzaldehyde With dmap; dicyclohexyl-carbodiimide In dichloromethane for 0.5h; Stage #2: p-(benzyloxy)benzoic acid In dichloromethane at 20℃; for 24h;	2.2-1 2-1: Preparation of 3-formylphenyl-4-(benzyloxy)benzoate 10.0 g (81.9 mmol) of 3-hydroxybenzaldehyde, 16.9 g (81.9 mmol) of N,N'-dicyclohexylcarbodiimide (DCC) and 1.00 g (8.19 mmol) of 4-dimethylaminopyridine (DMAP) was dissolved in 400 mL of dichloromethane, followed by stirring for 30 minutes. 18.7 g (81.9 mmol) of 4-(benzyloxy) benzoic acid was added and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, the mixture was filtered to remove urea, the remaining urea was removed by washing three times with distilled water. The solvent was distilled off under reduced pressure, column chromatography was performed using a single solvent of dichloromethane as a developing solvent. The solvent was distilled off under reduced pressure, completely dissolved in a small amount of dichloromethane, methanol was added to precipitate and 3-formylphenyl 4-(benzyloxy) benzoate which is a solid in the form of a white powder, was obtained. Yield: 84.2%.

81.2%

With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 24h;

1-1.3 (3) Preparation of compound of formula 1-3 To a solution of 3-hydroxybenzaldehyde (4.00 g, 32.75 mmol), N, N'-dicyclohexylcarbodiimide (6.76 g, 32.75 mmol) and 4-dimethylaminopyridine (0.40 g, 3.28 mmol) in 200 mL of dichloromethane After dissolution, 4- (benzyloxy) benzoic acid (7.48 g, 32.75 mmol) was added and stirred at room temperature for 24 hours. After completion of the reaction, the urea formed by filtration was filtered out and washed with distilled water three times to remove residual urea. The remaining filtrate was distilled under reduced pressure, and the obtained product was recrystallized from ethanol to obtain a white solid compound (1-3) (yield: 81.2%).

Reference： [1]Zhu, Chenhui; Shao, Renfan; Reddy, R. Amaranatha; Chen, Dong; Shen, Yongqiang; Gong, Tao; Glaser, Matthew A.; Korblova, Eva; Rudquist, Per; MacLennan, Joseph E.; Walba, David M.; Clark, Noel A. [Journal of the American Chemical Society, 2012, vol. 134, # 23, p. 9681 - 9687]
[2]Current Patent Assignee: KUMOH NATIONAL INSTITUTE OF TECHNOLOGY INDUSTRY; KYUNGPOOK NATIONAL UNIVERSITY - KR2016/126287, 2016, A Location in patent: Paragraph 0123-0125
[3]Current Patent Assignee: KUMOH NATIONAL INSTITUTE OF TECHNOLOGY INDUSTRY - KR2016/126298, 2016, A Location in patent: Paragraph 0082-0085
[4]Current Patent Assignee: KUMOH NATIONAL INSTITUTE OF TECHNOLOGY INDUSTRY; DONGJIN SEMICHEM CO.,LTD. - KR2015/80120, 2015, A Location in patent: Paragraph 0086; 0097; 0098

54
2-Amino-5-(4-methyl-phenyl)-thiophene-3-carboxylic Acid Amide [ No CAS ]
[ 1486-51-7 ]
[ 1393911-79-9 ]

Yield	Reaction Conditions	Operation in experiment
98%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In chloroform at 120℃; for 0.333333h; Microwave irradiation;	To a mixture of 2-amino-5-(4-methylphenyl) thiophene-3-carboxamide 1a (0.25 g, 0.107 mol) and 4-benzyloxy benzoic acid 4a (0.319 g, 0.140 mol) in anhydrous chloroform (4 ml) was added triethylamine (0.32 g, 0.323 mol) and phosphonic acid cyclic anhydride (1.02 g, 0.323 mol). The reaction mixture was irradiated at 120 °C in a microwave initiator for a given period of time (Table 1, entry 1). Once the substrate was completely consumed as monitored by TLC, the brown reaction mixture was cooled and poured into ice-cold water (10 ml). The product was extracted with ethyl acetate (2 × 25 ml) and the combined organic phase was washed with water, brine solution and dried over anhydrous sodium sulfite. The solvent was removed under vacuum and the brown residue was passed through a small plug of silica gel using petroleum ether/ethyl acetate (9/1) to afford 429 mg (94%) of 2a as a yellow solid.

Reference： [1]Location in patent: experimental part Poojari, Subba; Parameswar Naik; Krishnamurthy [Tetrahedron Letters, 2012, vol. 53, # 35, p. 4639 - 4643]

55
[ 1486-51-7 ]
cis-1,2,3,4-tetrahydro-naphthalene-2,3-diol [ No CAS ]
C₃₈H₃₂O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 12h;	1; 2.k Diol 12 (50 mg, 0.3 mmol), 4-benzyloxybenzoic acid (291 mg, 0.61 mmol), dicyclohexylcarbodiimide (263 mg, 0.61 mmol) and 4-dimethylaminopyridine (9 mg, 0.07 mmol) were dissolved in dry DCM and stirred at room temperature for 12 h. The DCM was removed and EtOAc was added and kept in the freezer for 12 h. The formed precipitate was filtered off and the crude product was purified by column chromatography to give the product as a white solid, m.p. 134°C, (1 15 mg, 64% yield): NMR (400 MHz, CDC13) δ: 3.23 - 3.4 (m, 4H), 5.09 (2, 4H), 5.67 (t, 2H), 6.93 (d, 4H), 7.14 - 7.41 (m, 14H), 7.92 (d, 4H); 13C NMR (500 MHz, CDC13) 5: 165.6, 162.5, 136.1, 132.5, 131.7, 129.1, 128.6, 128.2, 127.4, 126.4, 122.7, 1 14.4, 70.0, 69.9, 32.2; ESI MS m/z 607 (M + Na); HRMS (ESI) m/z, calculated for (M + Na) C38 H32 06 Na,

Reference： [1]Current Patent Assignee: WAYNE STATE UNIVERSITY; MCGILL UNIVERSITY; HONG KONG POLYTECHNIC UNIVERSITY - WO2012/171114, 2012, A1 Location in patent: Page/Page column 47; 59; 60

56
[ 1486-51-7 ]
[ 98-80-6 ]
[ 54589-41-2 ]

Yield	Reaction Conditions	Operation in experiment
70%	Stage #1: p-(benzyloxy)benzoic acid With potassium phosphate In 1,4-dioxane at 20℃; for 0.0833333h; Inert atmosphere; Stage #2: With 2-chloro-1,3-dimethylimidazolinium chloride In 1,4-dioxane at 20℃; for 2h; Inert atmosphere; Stage #3: phenylboronic acid With tetrakis(triphenylphosphine) palladium⁽⁰⁾ In 1,4-dioxane at 90℃; for 16h; Inert atmosphere; Sealed tube;	General procedure: General procedure: To a glass vial were added benzoic acid (500 mg, 4.094 mmol,1.0 equiv), K3PO4 (3.04 g, 14.33 mmol, 3.5 equiv) in 1,4-dioxane (12 mL). This reaction mixture was stirred for 5 min at rt under nitrogen atmosphere. After this 2-chloro-1,3-dimethyl imidazolidinium chloride (830 mg, 4.91 mmol,1.2 equiv) was added to the reaction mixture and stirred for 2 h at rt. To this reaction mixture was added phenyl boronic acid (750 mg, 6.14 mmol, 1.5 equiv) and tetrakis(triphenylphosphine)palladium (95 mg, 0.08 mmol, 0.02 equiv).Reaction was purged again with nitrogen for 5 min. Vial was sealed and heated at 90 C for 16 h. The reaction mixture was cooled to rt, filtered through Celite bed, and washed with ethyl acetate. Filtrate was concentrated under vacuum. The resulting material was purified by flash chromatography on Combiflash using 12g SNAP cartridge and eluted with 0-5% ethyl acetate in hexane to give benzophenone (522 mg, 70% yield).

Reference： [1]Pathak, Arunendra; Rajput, Chatrasal S.; Bora, Pushkar S.; Sharma, Somesh [Tetrahedron Letters, 2013, vol. 54, # 17, p. 2149 - 2150]

57
[ 1486-51-7 ]
[ 298-59-9 ]
C₂₈H₂₉NO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78.5%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In tetrahydrofuran for 96h;	Methylphenidate hydrochloride (2.698 g, 10 mmol), 4-benzyloxybenzoic acid (2.282 g, 10 mmol) and HOBt-H20 (1 .532 g, 10 mmol) in THF (60 mL) were added to Et3N (3.07 mL, 22 mmol), followed by 1 -ethyl-3-(3-dimethylaminopropyl) carbodiimide) hydrochloride (EDCI) (2.109 g, 1 1 mmol). The mixture was stirred for 4 days. EtOAc (200 mL) was added and the mixture was washed with water (30 mL), 5% HOAc (50 mL) and brine (40 mL). The EtOAc layer was dried over Na2SO4. The solvent was evaporated and the residue was crystallized from EtOAc (12 mL). The solid was collected by filtration and washed with cold EtOAc (3 x 4 mL) to give 53 (3.48 g) (yield, 78.5%) as a white solid.
78.5%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In tetrahydrofuran for 96h;	A A. Synthesis of BnO-p-salicylate-MPH (53) A. Synthesis of BnO-p-salicylate-MPH (53), the structure of which is shown below: (0340) Methylphenidate hydrochloride (2.698 g, 10 mmol), 4-benzyloxybenzoic acid (2.282 g, 10 mmol) and HOBt.H2O (1.532 g, 10 mmol) in THF (60 mL) were added to Et3N (3.07 mL, 22 mmol), followed by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide) hydrochloride (EDCI) (2.109 g, 11 mmol). The mixture was stirred for 4 days. EtOAc (200 mL) was added and the mixture was washed with water (30 mL), 5% HOAc (50 mL) and brine (40 mL). The EtOAc layer was dried over Na2SO4. The solvent was evaporated and the residue was crystallized from EtOAc (12 mL). The solid was collected by filtration and washed with cold EtOAc (3×4 mL) to give 53 (3.48 g) (yield, 78.5%) as a white solid.

Reference： [1]Current Patent Assignee: KEMPHARM INC - WO2013/16668, 2013, A2 Location in patent: Paragraph 00306
[2]Current Patent Assignee: KEMPHARM INC - US2015/266911, 2015, A1 Location in patent: Paragraph 0340

58
[ 30235-26-8 ]
[ 1486-51-7 ]
2-[(4-benzyloxybenzoyl)amino]-4-(pyridin-2-yl)thiazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%		General procedure: 5.1.3. General procedure C. To the carboxylic acid substrate (0.42 mmol, 1.2 equiv) in DMF (1.5 mL) was added CDI (0.50 mmol, 1.1equiv) and DBU (0.67 mmol, 1.9 equiv). The reaction was stirred for 30 min at 23 C. Next, 2-amino-4-(2-pyridyl)thiazole 20 (0.35 mmol, 1.0 equiv) was added and the reaction mixture was stirred for 16 h at 23 C. A small amount of silica gel was added to the reaction mixture, which was concentrated in vacuo under reduced pressure. The crude product impregnated on the silica gel was purified by silica gel flash chromatography (0-10% MeOH-CH2Cl2) to afford the title compound.

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 6385 - 6397

59
[ 771579-27-2 ]
[ 1486-51-7 ]
4-(benzyloxy)-N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30%	Stage #1: p-(benzyloxy)benzoic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 1h; Stage #2: 3-(aminomethyl)-4,6-dimethylpyridin-2-ol In dichloromethane at 20℃;	17.3 4-(benzyloxy)-N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)benzamide. 4-(benzyloxy)-N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)benzamide. To a solution of 4-(benzyloxy)benzoic acid (228 mg, 1 mmol), N-(3-dimethylaminopropyl)-N'- ethylcarbodiimide hydrochloride (210 mg, 1.1 mmol) and hydroxybenzotriazole (149 mg, 1.1 mmol) in dichloromethane (30 mL) was added triethylamine (202 mg, 2 mmol). The reaction mixture was stirred at room temperature for 1 hour, then 3-aminopropanenitrile (156 mg, 1 mmol) was added. The reaction mixture was stirred at room temperature overnight. After the reaction, the mixture was washed with saturated solution of sodium bicarbonate (10mL><3), dried over anhydrous sodium sulfate to give crude product which was purified by column chromatography (silica gel, dichloromethane/methanol = 50: 1) to give 4-(benzyloxy)-N-((2- hydroxy-4,6-dimethyl pyridin-3-yl)methyl)benzamide (Compound 1-12) (110 mg, 30%). LRMS (M + H+) m/z: calcd 451.11 ; found 451. 1H NMR (300 MHz, /-DMSO) 511.47 (s, 1H), 8.20 (s, 1H), 7.82 (d, J = 8.7 Hz, 2H), 7.49-7.35 (m, 5H), 7.05 (d, J = 8.7 Hz, 2H), 5.88 (s, 1H), 5.17 (s, lH), 4.30 (d, J = 4.S H 2H), 2.19 (s, lH), 2.13 (s, 1H).
30%	Stage #1: p-(benzyloxy)benzoic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 1h; Stage #2: 3-(aminomethyl)-4,6-dimethylpyridin-2-ol In dichloromethane at 20℃;	17 4-(benzyloxy)-N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)benzamide To a solution of 4-(benzyloxy)benzoic acid (228 mg, 1 mmol), N-(3-dimethylaminopropyl)-N’-ethylcarbodiimidehydrochloride (210mg, 1.1 mmol) and hydroxybenzotriazole (149 mg, 1.1 mmol) in dichioromethane (30 mE) was added triethylamine (202 mg, 2 mmol). The reaction mixture was stirred at room temperature for 1 hour, then 3 -aminopropanenitrile (156 mg, 1 mmol) was added. The reaction mix-ture was stirred at room temperature overnight. Afier the reaction, the mixture was washed with saturated solution of sodium bicarbonate (10 mEx3), dried over anhydrous sodium sulfate to give crude product which was purified by column chromatography (silica gel, dichloromethane/methanol=50:1) to give 4-(benzyloxy)-N-((2-hydroxy-4,6-dimethylpyri- din-3-yl)methyl)benzamide (Compound 1-12) (110 mg, 30%). ERMS (M+H) mlz: calcd 451.11. found 451. ‘H NMR (300 MHz, d6-DMSO) oil .47 (s, 1H), 8.20 (s, 1H), 7.82 (d, J=8.7 Hz, 2H), 7.49-7.35 (m, 5H), 7.05 (d, J=8.7 Hz, 2H), 5.88 (s, 1H), 5.17 (s, 1H), 4.30 (d, J=4.8 Hz, 2H), 2.19 (s, 1H), 2.13 (s, 1H).

Reference： [1]Current Patent Assignee: MORPHOSYS AG - WO2013/75083, 2013, A1 Location in patent: Paragraph 00210; 00212
[2]Current Patent Assignee: MORPHOSYS AG - US9206128, 2015, B2 Location in patent: Page/Page column 118; 119

60
[ 5177-27-5 ]
[ 1486-51-7 ]
[ 1431535-75-9 ]

Yield	Reaction Conditions	Operation in experiment
		A) tert-butyl ((2S)-4-(2-(4-(benzyloxy)phenyl)[1,3]oxazolo[5,4-d]pyrimidin-5-yl)but-3-yn-2-yl)carbamate A mixture of 4-(benzyloxy)benzoic acid (1.04 g) and phosphorus oxychloride (12.2 mL) was stirred at room temperature for 5 min, and <strong>[5177-27-5]2,4-dichloropyrimidin-5-amine</strong> (500 mg) was added thereto, and the obtained mixture was stirred at 100 C. for 2 hr. The reaction mixture was added to 1M aqueous sodium hydroxide solution at 0 C., and the precipitate was collected by filtration, and dissolved in THF and ethyl acetate. The obtained solution was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give 2-(4-(benzyloxy)phenyl)-5-chloro[1,3]oxazolo[5,4-d]pyrimidine (3.07 g) as a mixture with impurity.

Reference： [1]Patent: US2014/243310,2014,A1 .Location in patent: Paragraph 1725

61
[ 1486-51-7 ]
[ 28084-48-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 0 °C 2: palladium 10% on activated carbon; hydrogen / tetrahydrofuran / 20 °C

Reference： [1]Garcia-Marquez, Alfonso Ramon; Heinrich, Benoit; Beyer, Nicolas; Guillon, Daniel; Donnio, Bertrand [Macromolecules, 2014, vol. 47, # 15, p. 5198 - 5210]

62
[ 1486-51-7 ]
2-(morphorin-4-yl)-2-phenylethanamine dihydrochloride [ No CAS ]
C₂₆H₂₈N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71.6%	With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 0 - 20℃; for 18h;	61 Preparative Example 61: Preparation of compound represented by Formula 62 (VVZ-081 4-benzyloxybenzoic acid represented by Formula 140 (150 mg, 0.657 mmol, purchased from TCI Co.) was slowly added to 2-morpholin-2-yl-2-phenylethanamine dihydrochloride represented by Formula 111 (183.5 mg, 0.657 mmol, purchased from Matrix Co.) and diisopropylethylamine (0.344 mL, 1.972 mmol) in DMF (10 mL) at room temperature. After cooling the reaction mixture to 0°C and adding 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate methanaminium (HATU, 249.9 mg, 0.657 mmol) thereto, the mixture was agitated at room temperature for 18 hours. The reaction solvent was removed under reduced pressure and chloroform/methanol (9:1, v/v) was added to the remaining concentrate to prepare a solution. The solution was washed with a potassium carbonate (K2CO3) solution, followed by separation to form an organic layer. After drying the organic layer with magnesium sulfate (MgSO4), the solvent was removed again under reduced pressure. The obtained vacuum-concentrated mixture was subjected to separation and purification through column chromatography (chloroform/methanol, 10:1, v/v) using silica gel (SiO2). As a result, a benzamide compound represented by Formula 62 was produced (WZ-081; 196 mg, 71.6% yield). [0289] Analysis data of the produced benzamide compound is provided as follows. Rf(ethyl acetate/n-hexane/triethylamine, 2:1/0.1, v/v/v) 0.47; 1H NMR (500 MHz, MeOD-d4) δ 2.51 (s, 4 H), 3.57-3.62 (m, 1 H), 3.67-3.73 (m, 5 H), 3.98-4.02 (m, 1 H), 5.15 (s, 2 H), 7.00-7.02 (m, 2 H), 7.28-7.44 (m, 10 H), 7.61-7.64 (m, 2 H).
71.6%	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 0 - 20℃; for 18h;	P.61 Preparation of Compound Represented by Formula 62 (VVZ-081) 4-benzyloxybenzoic acid represented by Formula 140 (150 mg, 0.657 mmol, purchased from TCI Co.) was slowly added to 2-morpholin-2-yl-2-phenylethanamine dihydrochloride represented by Formula 111 (183.5 mg, 0.657 mmol, purchased from Matrix Co.) and diisopropylethylamine (0.344 mL, 1.972 mmol) in DMF (10 mL) at room temperature. After cooling the reaction mixture to 0° C. and adding 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate methanaminium (HATU, 249.9 mg, 0.657 mmol) thereto, the mixture was agitated at room temperature for 18 hours. The reaction solvent was removed under reduced pressure and chloroform/methanol (9:1, v/v) was added to the remaining concentrate to prepare a solution. The solution was washed with a potassium carbonate (K2CO3) solution, followed by separation to form an organic layer. After drying the organic layer with magnesium sulfate (MgSO4), the solvent was removed again under reduced pressure. The obtained vacuum-concentrated mixture was subjected to separation and purification through column chromatography (chloroform/methanol, 10:1, v/v) using silica gel (SiO2). As a result, a benzamide compound represented by Formula 62 was produced (VVZ-081; 196 mg, 71.6% yield). Analysis data of the produced benzamide compound is provided as follows. Rf (ethyl acetate/n-hexane/triethylamine, 2:1/0.1, v/v/v) 0.47; 1H NMR (500 MHz, MeOD-d4) δ 2.51 (s, 4H), 3.57-3.62 (m, 1H), 3.67-3.73 (m, 5H), 3.98-4.02 (m, 1H), 5.15 (s, 2H), 7.00-7.02 (m, 2H), 7.28-7.44 (m, 10H), 7.61-7.64 (m, 2H)

Reference： [1]Current Patent Assignee: VIVOZON - EP2786986, 2014, A2 Location in patent: Paragraph 0287-0288
[2]Current Patent Assignee: VIVOZON - US2014/336378, 2014, A1 Location in patent: Paragraph 0437 - 0441

63
[ 1486-51-7 ]
[ 19968-85-5 ]
C₂₁H₂₅NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 0 - 20℃; for 24h;	48 Preparative Example 48: Preparation of compound represented by Formula 49 (VVZ-048) The same procedures as described in Preparative Example 2 were conducted, and a compound represented by Formula 140, that is, 4-benzyloxybenzoic acid (119.42 mg, 0.523 mmol) and 1-aminomethyl-1-cyclohexanol hydrochloride represented by Formula 93 (78.8 mg, 0.476 mmol) were used according to reaction scheme 49. As a result, a benzamide compound represented by Formula 49 was obtained as a desired product (WZ-048; 142.10 mg, 88.0% yield). [0251] Analysis data of the produced benzamide compound is provided as follows. 1H-NMR (MeOD-d4) d 1.32∼1.69(m, 10H), 3.40(s, 2H), 5.16(s, 2H), 7.05∼7.83(m, 9H).

Reference： [1]Current Patent Assignee: VIVOZON - EP2786986, 2014, A2 Location in patent: Paragraph 0249-0251

64
[ 1486-51-7 ]
4-(aminomethyl)-1-methylpiperidin-4-ol dihydrochloride [ No CAS ]
C₂₁H₂₆N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73.1%	With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 0 - 20℃; for 24h;	51 Preparative Example 51: Preparation of compound represented by Formula 52 (VVZ-056) The same procedures as described in Preparative Example 2 were conducted, and a compound represented by Formula 140, that is, 4-benzyloxybenzoic acid (54.23 mg, 0.238 mmol) and a compound represented by Formula 142, that is, 4-(aminomethyl)-1-methylpiperidin-4-ol dihydrochloride (46.9 mg, 0.216 mmol) were used according to reaction scheme 52. As a result, a benzamide compound represented by Formula 52 was obtained as a desired product (WZ-056; 56.00 mg, 73.1 % yield). [0260] Analysis data of the produced benzamide compound is provided as follows. 1H-NMR (MeOD-d4) d 1.67(m, 4H), 2.29(s, 3H), 2.41(m, 2H), 2.62(m, 2H), 3.32(s, 2H), 5.16(s, 2H), 7.05∼7.83(m, 9H).

Reference： [1]Current Patent Assignee: VIVOZON - EP2786986, 2014, A2 Location in patent: Paragraph 0258-0260

65
[ 330792-70-6 ]
[ 1486-51-7 ]
(R)-tert-butyl 3-(5-amino-3-(4-(benzyloxy)phenyl)-4-cyano-1H-pyrazol-1-yl)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In N,N-dimethyl-formamide; at 20 - 75℃; for 35h;	General procedure: To a solution of tert-butyl 3-(tosyloxy)piperidine-1-carboxylate (355 mg, 1.0 mmol) and <strong>[330792-70-6]5-amino-3-(4-phenoxyphenyl)-1H-pyrazole-4-carbonitrile</strong> (276 mg, 1.0 mmol) in 5 mL of DMF was added Cs2CO3 (650 mg, 2.0 mmol). The mixture was stirred at RT for 16 h, 75° C. for 3 h and 60° C. for 16 h. The mixture was concentrated washed with brine (100 mL×3) and dried over Na2SO4. Concentrated and purified by chromatography column on silica gel (eluted with PE/EA=3/1) to afford 60 mg (13percent) of tert-butyl 3-(5-amino-4-cyano-3-(4-phenoxyphenyl)-1H-pyrazol-1-yl)piperidine-1-carboxylate as a yellow oil. The desired product was prepared from 4-(benzyloxy)benzoic acid and according to the similar procedures in step 1 to step 5 of tert-butyl 3-(5-amino-4-cyano-3-(4-phenoxyphenyl)-1H-pyrazol-1-yl)piperidine-1-carboxylate under appropriate conditions recognized by one of ordinary skill in the art. 1H NMR (400 MHz, DMSO-d6) delta 7.78 (d, J=8.8 Hz, 2H), 7.60-7.36 (m, 5H), 7.17 (d, J=8.8 Hz, 2H), 6.81 (s, 2H), 5.21 (s, 2H), 4.32-4.18 (m, 1H), 4.00-3.75 (m, 2H), 3.02-2.84 (m, 1H), 2.04-1.87 (m, 3H), 1.65-1.35 (m, 2H), 1.45 (s, 9H).

Reference： [1]Patent: US2015/5277,2015,A1 .Location in patent: Paragraph 0137; 0138; 0179; 0180

66
[ 13035-19-3 ]
[ 1486-51-7 ]
4-benzyloxy-N-(4-piperidyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
18%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 15h;	4-Aminopiperidine (215 mg, 2.15 mmol, 1.0 eq) [13035-19-3] is added at room temperature to a stirred solution of 4-benzyloxybenzoic acid (500 mg, 2.15 mmol, 1.0 eq) [1486-51-7] in N,N-dimethylformamide (10 mL), followed by N-(3-dimethylaminopropyl)-N?-ethylcarbodiimide hydrochloride (482 mg, 1.15 eq, 2.47 mmol), 1-hydroxybenzotriazole (362 mg, 2.36 mmol, 1.1 eq) and N,N-diisopropylethylamine (1.87 mL, 10.73 mmol, 5.0 eq). After 15 hours stirring at room temperature, solvent is evaporated and the residue is extracted with dichloromethane (3 x 20 mL) and water (20 mL). The combined organic layers are washed with brine (20 mL), dried over sodium sulfate, filtered and concentrated to give a residue that is purified by column chromatography (silica gel; dichloromethane:methanol, 9:1, v/v) to afford 4-benzyloxy-N-(4- piperidyl)benzamide as a yellow amorphous (130 mg, 18% yield).

Reference： [1]Patent: WO2016/198691,2016,A1 .Location in patent: Page/Page column 170

67
[ 1486-51-7 ]
[ 171364-78-6 ]

Reference： [1]Angewandte Chemie - International Edition,2017,vol. 56,p. 2482 - 2486
Angew. Chem.,2017,vol. 129,p. 2522 - 2526,5

68
[ 1486-51-7 ]
[ 75178-96-0 ]
tert-butyl N-[3-[(4-benzyloxybenzoyl)amino]propyl]carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 18 - 25℃; for 15h; Inert atmosphere;	6 Preparation of tert-butyl N- 13- F(4-benzvloxvbenzovl)aminolpropvllcarbamate: tert-Butyl N-(3-aminopropyl)carbamate (374 mg, 2.15 mmol, 1.0 eq) [75178-96-0] is added at room temperature to a stirred solution of 4-benzyloxybenzoic acid (500 mg, 2.15 mmol, 1.0 eq) [1486-51-7] inN,N-dimethylformamide (10 mL), followed by N-(3 -dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (482 mg, 2.47 mmol, 1.15 eq), i-hydroxybenzotriazole (362 mg, 2.36 mmol, 1.1 eq) and N,N diisopropylethylamine (1.87 mL, 10.73 mmol, 5.0 eq). After 15 hours stirring at room temperature, solvent is evaporated and the residue is extracted with dichloromethane (3 x 20 mL) and water (20 mL). The combined organic layers are washed with brine (20 mL), dried over sodium sulfate, filtered and concentrated to give a residue that is purified by column chromatography (silica gel; dichloromethane:methanol, 9:1, v/v) to affordtert-butyl N-[3-[(4-benzyloxybenzoyl)amino]propyl]carbamate as a white solid (700 mg, 80% yield). MS mlz (+ESI): 385.4 [M+H].

Reference： [1]Current Patent Assignee: BASILEA PHARMACEUTICA - WO2017/42099, 2017, A1 Location in patent: Page/Page column 69; 84; 85

69
[ 1486-51-7 ]
3,4,5-trifluorophenyl 3-[(4-hydroxy)benzoyloxy]benzoate [ No CAS ]
3-(3,4,5-trifluorophenylcarboxy)phenyl-4-[4-(benzyloxy)benzoyloxy]benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92.8%	Stage #1: p-(benzyloxy)benzoic acid; 3,4,5-trifluorophenyl 3-[(4-hydroxy)benzoyloxy]benzoate With dmap In dichloromethane for 0.5h; Inert atmosphere; Stage #2: With dicyclohexyl-carbodiimide In dichloromethane for 24h; Inert atmosphere;	2-5 prearation of 3- (3,4,5-trifluorophenylcarboxy) phenyl 4- [4- (benzyloxy) benzoyloxy] benzoate 10.4 g (26.9 mmol) of the 3,4,5-trifluorophenyl 3 - [(4-hydroxy) benzoyloxy] benzoate obtained above, 7.36 g (32.2 mmol) of 4- (benzyloxy) benzoic acid and 0.33 g (2.69 mmol) of DMAP were dissolved in MC and stirred for 30 minutes under a nitrogen atmosphere., 6.65 g (32.2 mmol) of DCC was added, and the mixture was stirred under a nitrogen atmosphere for 24 hours. After the completion of the reaction, the resulting urea was filtered off the filter paper, washed three times with an aqueous solution of NaCl and distilled water, and then distilled under reduced pressure, and column chromatography was performed using a single solvent of dichloromethane as a developing solvent. The solution thus obtained was distilled under reduced pressure and then vacuum dried to obtain 3- (3,4,5-trifluorophenylcarboxy) phenyl 4- [4- (benzyloxy) benzoyloxy] benzoate as a white solid product
78%	Stage #1: 3,4,5-trifluorophenyl 3-[(4-hydroxy)benzoyloxy]benzoate With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 0.5h; Inert atmosphere; Stage #2: p-(benzyloxy)benzoic acid In dichloromethane at 20℃; for 24h;	2.2-5 2-5: Preparation of 3-(3,4,5-trifluorophenylcarboxy)phenyl-4-[4-(benzyloxy)benzoyloxy]benzoate The obtained 7.60 g (19.6 mmol) of 3,4,5-trifluorophenyl-3-[(4-hydroxy) benzoyloxy] benzoate, 4.04 g (19.6 mmol) DCC and 0.23 g (1.94 mmol) of DMAP were dissolved in 300 ml of dichloromethane. The solution was stirred at room temperature for 30 minutes under a nitrogen atmosphere. 4.47 g (19.6 mmol) of 4-(benzyloxy) benzoic acid was added, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, the urea was filtered out. The remaining urea was removed by washing three times with distilled water. The solvent was distilled off under reduced pressure. Column chromatography was performed using a single solvent of dichloromethane as a developing solvent. Next, the solvent was distilled off under reduced pressure, and dissolved in a small amount of dichloromethane, methanol was added to precipitate 3-(3,4,5-trifluorophenylcarboxy)phenyl-4-[4-(benzyloxy) benzoyloxy] benzoate, a solid in the form of a white powder, was obtained.

Reference： [1]Current Patent Assignee: KUMOH NATIONAL INSTITUTE OF TECHNOLOGY INDUSTRY; KYUNGPOOK NATIONAL UNIVERSITY - KR2016/126287, 2016, A Location in patent: Paragraph 0139-0141
[2]Current Patent Assignee: KUMOH NATIONAL INSTITUTE OF TECHNOLOGY INDUSTRY - KR2016/126298, 2016, A Location in patent: Paragraph 0099-0102

70
[ 1486-51-7 ]
2,4,6-trifluorophenyl 3-[4-(hydroxy)benzoyloxy]benzoate [ No CAS ]
3-(2,4,6-trifluorophenylcarboxy)phenyl-4-[4-(benzyloxy)benzoyloxy]benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96.5%	Stage #1: p-(benzyloxy)benzoic acid; 2,4,6-trifluorophenyl 3-[4-(hydroxy)benzoyloxy]benzoate With dmap In dichloromethane for 0.5h; Inert atmosphere; Stage #2: With dicyclohexyl-carbodiimide In dichloromethane for 24h; Inert atmosphere;	3-3 23.6 g (60.7 mmol) of the obtained 2,4,6-trifluorophenyl 3 - [(4-hydroxy) benzoyloxy] benzoate,16.6 g (72.7 mmol) of 4- (benzyloxy) benzoic acid and 0.74 g (6.07 mmol) of DMAP were dissolved in MC, And then 15.0 g (72.7 mmol) of DCC was added thereto, followed by stirring under a nitrogen atmosphere for 24 hours. After the completion of the reaction, the resulting urea was filtered off the filter paper, washed three times with an aqueous solution of NaCl and distilled water, and then distilled under reduced pressure, and column chromatography was performed using a single solvent of dichloromethane as a developing solvent. The solution thus obtained was distilled under reduced pressure, vacuum-driedto obtain a solid product, 3- (2,4,6-trifluorophenylcarboxy) phenyl 4- [4- (benzyloxy) benzoyloxy] benzoate
88.4%	Stage #1: 2,4,6-trifluorophenyl 3-[4-(hydroxy)benzoyloxy]benzoate With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 0.5h; Inert atmosphere; Stage #2: p-(benzyloxy)benzoic acid In dichloromethane at 20℃; for 24h;	4.4-3 4-3: Preparation of 3-(2,4,6-trifluorophenylcarboxy)phenyl-4-[4-(benzyloxy)benzoyloxy]benzoate 2.50 g (6.43 mmol) of 2,4,6-trifluorophenyl-3-[(4-hydroxy)benzoyloxy] benzoate obtained above, 1.46 g (6.43 mmol) of DCC and 0.07 g (0.64 mmol) of DMAP were dissolved in 200 ml of dichloromethane. The solution was stirred at room temperature for 30 minutes under a nitrogen atmosphere. Next, 1.46 g (6.43 mmol) of 4-(benzyloxy) benzoic acid was added, and the mixture was stirred at room temperature for 24 hours. After completion of the reaction, the urea was filtered out. The remaining urea was removed by washing three times with distilled water. The solvent was distilled off under reduced pressure, column chromatography was performed using a single solvent of dichloromethane as a developing solvent. Next, the solvent was distilled off under reduced pressure, completely dissolved in a small amount of dichloromethane, methanol was added to precipitate, and 3-(2,4,6-trifluorophenylcarboxy)phenyl-4-[4-(benzyloxy)benzoyloxy] benzoate, a solid in the form of a white powder, was obtained. Yield: 88.4%.

Reference： [1]Current Patent Assignee: KUMOH NATIONAL INSTITUTE OF TECHNOLOGY INDUSTRY; KYUNGPOOK NATIONAL UNIVERSITY - KR2016/126287, 2016, A Location in patent: Paragraph 0156-0158
[2]Current Patent Assignee: KUMOH NATIONAL INSTITUTE OF TECHNOLOGY INDUSTRY - KR2016/126298, 2016, A Location in patent: Paragraph 0120-0123

71
[ 1486-51-7 ]
[ 188637-63-0 ]
4-(benzyloxy)-N-((6-bromopyridin-2-yl)methyl)benzamide [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2017,vol. 82,p. 5046 - 5067

72
[ 1486-51-7 ]
[ 128958-65-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate / neat (no solvent) / 120 °C / Sealed tube
	Multi-step reaction with 2 steps 1: sulfuric acid / Reflux 2: hydrazine hydrate / neat (no solvent) / 120 °C / Sealed tube
	Multi-step reaction with 2 steps 1: sulfuric acid / 5 h / Reflux 2: hydrazine hydrate / ethanol / 100 °C / Sealed tube

Multi-step reaction with 2 steps 1: sulfuric acid / 5 h / Reflux 2: hydrazine hydrate / ethanol / 100 °C / Sealed tube

Reference： [1]Sevaille, Laurent; Gavara, Laurent; Bebrone, Carine; De Luca, Filomena; Nauton, Lionel; Achard, Maud; Mercuri, Paola; Tanfoni, Silvia; Borgianni, Luisa; Guyon, Carole; Lonjon, Pauline; Turan-Zitouni, Gülhan; Dzieciolowski, Julia; Becker, Katja; Bénard, Lionel; Condon, Ciaran; Maillard, Ludovic; Martinez, Jean; Frère, Jean-Marie; Dideberg, Otto; Galleni, Moreno; Docquier, Jean-Denis; Hernandez, Jean-François [ChemMedChem, 2017, vol. 12, # 12, p. 972 - 985]
[2]Baud, Damien; Bebrone, Carine; Becker, Katja; Benvenuti, Manuela; Cerboni, Giulia; Chelini, Giulia; Cutolo, Giuliano; De Luca, Filomena; Docquier, Jean-Denis; Feller, Georges; Fischer, Marina; Galleni, Moreno; Gavara, Laurent; Gresh, Nohad; Kwapien, Karolina; Legru, Alice; Mangani, Stefano; Mercuri, Paola; Pozzi, Cecilia; Sannio, Filomena; Sevaille, Laurent; Tanfoni, Silvia; Verdirosa, Federica; Berthomieu, Dorothée; Bestgen, Benoît; Frère, Jean-Marie; Hernandez, Jean-François [European Journal of Medicinal Chemistry, 2020, vol. 208]
[3]Gavara, Laurent; Legru, Alice; Verdirosa, Federica; Sevaille, Laurent; Nauton, Lionel; Corsica, Giuseppina; Mercuri, Paola Sandra; Sannio, Filomena; Feller, Georges; Coulon, Rémi; De Luca, Filomena; Cerboni, Giulia; Tanfoni, Silvia; Chelini, Giulia; Galleni, Moreno; Docquier, Jean-Denis; Hernandez, Jean-François [Bioorganic Chemistry, 2021, vol. 113]
[4]Legru, Alice; Verdirosa, Federica; Hernandez, Jean-François; Tassone, Giusy; Sannio, Filomena; Benvenuti, Manuela; Conde, Pierre-Alexis; Bossis, Guillaume; Thomas, Caitlyn A.; Crowder, Michael W.; Dillenberger, Melissa; Becker, Katja; Pozzi, Cecilia; Mangani, Stefano; Docquier, Jean-Denis; Gavara, Laurent [European Journal of Medicinal Chemistry, 2021, vol. 226]

73
[ 1486-51-7 ]
[ 249566-74-3 ]
N-(3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-β-D-glucopyranosyl)-4-(benzyloxy)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	With benzotriazol-1-ol; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 20℃; for 96h;	7 4.1.7 N-(3,4,6-Tri-O-acetyl-2-deoxy-2-fluoro-β-d-glucopyranosyl)-4-(benzyloxy)benzamide (6) Coupling of amino-sugar 5 (500 mg, 1.63 mmol) with 4-benzyloxybenzoic acid (410 mg, 1.79 mmol) was carried out according to the DCC/HOBt general procedure in DMF (44 mL) and 4 days stirring. After filtration and evaporation under vacuum, the crude residue was purified by silica gel chromatography (petroleum ether/ethyl acetate, 5/5, v/v) to give compound 6 (382 mg, 45%): 1H NMR (200 MHz, CDCl3) δ 7.82 (d, 2H, J = 8.8 Hz, HAr), 7.42-7.36 (m, 5H, HAr), 7.20 (d, 1H, J = 9.3 Hz, NH), 7.00 (d, 2H, J = 8.8 Hz, HAr), 5.61 (td, 1H, J1,NH = J1,2 = 8.8 Hz, J1,F = 1.4 Hz, H-1), 5.43 (td, 1H, J2,3 = J3,4 = 9.2 Hz, J3,F = 13.7 Hz, H-3), 5.11 (s, 2H, CH2Ph), 5.06 (t, 1H, J3,4 = J4,5 = 9.7 Hz, H-4), 4.55 (td, 1H, J1,2, J2,3, J2,F = 49.9 Hz, H-2), 4.40 (dd, 1H, J6a,6b = 12.3 Hz, J5,6a = 4.0 Hz, H-6a), 4.04 (m, 1H, H-6b), 3.91 (ddd, 1H, J4,5, J5,6a, J5,6b = 1.8 Hz, H-5), 2.08, 2.06, 2.04 (each s, 3*3H, OAc); 13C NMR (50 MHz, CDCl3) δ 170.77, 170.16, 169.93, 167.14 (CO), 162.18 (CArO), 136.27 (CArCH2), 129.53, 128.81, 128.37, 127.60 (CHAr), 125.60 (CArCO), 114.88 (CHAr), 88.51 (C-2, J2,F = 190.5 Hz), 78.18 (C-1, J1,F = 22.4 Hz), 73.80-73.50 (C-3, C-5), 70.27 (CH2Ph), 68.11 (C-4, J4,F = 6.1 Hz), 61.63 (C-6), 20.73 (CH3); 19F NMR (CDCl3) δ -197.67.

Reference： [1]El Hilali, Mostafa; Reux, Bastien; Debiton, Eric; Leal, Fernand; Galmier, Marie-Josephe; Vivier, Magali; Chezal, Jean-Michel; Miot-Noirault, Elisabeth; Coudert, Pascal; Weber, Valérie [Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 20, p. 5692 - 5708]

74
4-[(4-propenoyloxy)butyloxy]benzoic acid [ No CAS ]
[ 95-71-6 ]
[ 1486-51-7 ]
C₄₂H₄₀O₁₂ [ No CAS ]
C₄₂H₄₀O₁₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-methylbenzene-1,4-diol; p-(benzyloxy)benzoic acid With toluene-4-sulfonic acid In 5,5-dimethyl-1,3-cyclohexadiene for 30h; Dean-Stark; Reflux; Stage #2: With 5%-palladium/activated carbon; hydrogen In tetrahydrofuran; ethanol at 50℃; for 5h; Autoclave; Stage #3: 4-[(4-propenoyloxy)butyloxy]benzoic acid Further stages;	2-12 (Example 2-12) Preparation of a compound represented by the formula (D-10C) In a reaction vessel equipped with a Dean-Stark apparatus and a condenser, 10.0 g of the compound represented by the formula (C-2C-1)18.4 g of the compound represented by the formula (C-2C-2)3.1 g of p-toluenesulfonic acid monohydrate and 200 mL of xylene were added,And heated under reflux for 30 hours while removing water.After cooling, the solid was filtered and washed with cold methanol. And dried to obtain 25.6 g of a compound represented by the formula (C-2C-3). In an autoclave, 25.6 g of the compound represented by the formula (C-2C-3)Tetrahydrofuran 300 mL,Ethanol 150 mL,0.3 g of 5% palladium carbon was added,And the mixture was heated and stirred for 5 hours at 50 ° C. under a hydrogen pressure of 0.5 MPa.After removal of palladium carbon, the solvent was distilled off and dried,To obtain 17.8 g of a compound represented by the formula (C-2C). In a reaction vessel equipped with a Dean-Stark apparatus and a condenser, 10.0 g of the compound represented by the formula (C-2A-1)11.1 g of the compound represented by the formula (C-2A-2)p-toluenesulfonic acid monohydrate3.1 g,200 mL of xylene was added,And heated under reflux for 30 hours while removing water.After cooling, the solid was filtered and washed with cold methanol.And dried to obtain 18.1 g of a compound represented by the formula (C-2A). Under a nitrogen atmosphere,To the reaction vessel, 1.0 g of methanesulfonyl chloride,Tetrahydrofuran 5 mL,10 mg of 2,6-di-tert-butyl-4-methylphenol was added.It was cooled to -5 ° C.,A solution prepared by dissolving 2.0 g of the compound represented by the formula (D-10A-1) in 10 mL of tetrahydrofuran and 1.3 g of diisopropylethylamine were added dropwise and stirred at -5 ° C. for 1 hour.9 mL of a tetrahydrofuran solution of 1.8 g of the compound represented by the formula (C-2A) produced in Example 1-2,1.3 g of diisopropylethylamine,10 mg of 4-dimethylaminopyridine was added,And the mixture was stirred at room temperature for 2 hours.The reaction solution was poured into water and extracted with dichloromethane.Purification was carried out by column chromatography (silica gel, dichloromethane) and recrystallization (dichloromethane / methanol)4.5 g of a compound represented by the formula (D-10A) was obtained.The obtained multi-compound has a purity of 99.431% (impurity content represented by formula (C-2A) of 0.002%, impurity content represented by formula (F1-10) and formula (F2-10) 0.012%). In Example 2-10, the compound represented by the formula (C-2A) was added to the compound represented by the formula (C-2C) produced in Example 1-4,By the same method except that the compound represented by the formula (D-10A-1) was replaced by the compound represented by the formula (D-10C-1)To prepare a compound represented by the formula (D-10C).The obtained compound had a purity of 98.735% (impurity content represented by formula (C-2C) 0.005%, impurity content represented by formula (F1-10) and formula (F2-10) 0.054%).

Reference： [1]Current Patent Assignee: DIC CORP. - JP2018/70546, 2018, A Location in patent: Paragraph 0224-0227; 0301-0303; 0305-0307

75
[ 95-71-6 ]
[ 1486-51-7 ]
C₁₄H₁₂O₄ [ No CAS ]
C₁₄H₁₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-methylbenzene-1,4-diol; p-(benzyloxy)benzoic acid With toluene-4-sulfonic acid In 5,5-dimethyl-1,3-cyclohexadiene for 30h; Dean-Stark; Reflux; Stage #2: With 5%-palladium/activated carbon; hydrogen In tetrahydrofuran; ethanol at 50℃; for 5h; Autoclave; Overall yield = 17.8 g;	1-4 In a reaction vessel equipped with a Dean-Stark apparatus and a condenser, 10.0 g of the compound represented by the formula (C-2C-1)18.4 g of the compound represented by the formula (C-2C-2)3.1 g of p-toluenesulfonic acid monohydrate and 200 mL of xylene were added,And heated under reflux for 30 hours while removing water.After cooling, the solid was filtered and washed with cold methanol. And dried to obtain 25.6 g of a compound represented by the formula (C-2C-3). In an autoclave, 25.6 g of the compound represented by the formula (C-2C-3)Tetrahydrofuran 300 mL,Ethanol 150 mL,0.3 g of 5% palladium carbon was added,And the mixture was heated and stirred for 5 hours at 50 ° C. under a hydrogen pressure of 0.5 MPa.After removal of palladium carbon, the solvent was distilled off and dried,To obtain 17.8 g of a compound represented by the formula (C-2C).

Reference： [1]Current Patent Assignee: DIC CORP. - JP2018/70546, 2018, A Location in patent: Paragraph 0224-0227

76
[ 100-69-6 ]
[ 1486-51-7 ]
C₂₁H₁₉NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%	With dipotassium hydrogenphosphate; [4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine-N1,N1′]bis{3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-κN]phenyl-κC}iridium(III) hexafluorophosphate; triphenylphosphine In dichloromethane; water at 20℃; Inert atmosphere; Irradiation;	3 Example 3 Firstly weighing (45.6 mg, 0.2 mmol), photocatalyst Ir[dF(CF3)ppy]2(dtbbpy)PF6(2.3mg, 0.002 mmol), K2HPO4(7.0 Mg, 0 . 04 mmol), and Ph3P (62.9 mg, 0 . 24 mmol) are added to a reaction tube, pumping air through the vacuum line three times, in the argon atmosphere, adding DCM/H2O (2.0 ml, 4:1 v/v), then carefully added (31.5 mg, 0.3 mmol), then put into 5 W blue LEDs lamp irradiation, react at room temperature for 36 - 60 h. Add 20 ml water, and the DCM extraction (3x 10 ml) the aqueous phase, combined with the organic phase. The organic phase by absolute Na2SO4After drying and steaming and to remove the solvent, dry sample, column chromatography (300 - 400 item of chromatographic analysis silica gel) (petroleum ether - ethyl acetate) to obtain the product 30.4 mg, Yield 48%.

Reference： [1]Current Patent Assignee: NANJING UNIVERSITY - CN108912042, 2018, A Location in patent: Paragraph 0022; 0023

77
[ 57260-73-8 ]
[ 1486-51-7 ]
C₂₁H₂₆N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With dmap; 1,2-dichloro-ethane In dichloromethane at 20℃;	3.1.1 General procedure for amide bond formation reaction (method A) General procedure: To a solution of the carboxyl compound (1.0 equiv.) in DCM, EDC (1.6 equiv.) and DMAP(0.25 equiv.) were added slowly. Then the amino compound (1.2 equiv.) was added to the mixture.The reaction mixture was stirred at room temperature for 1h and then washed with saturated saltsolution (50 mL × 3). The organic layer was collected and dried over Na2SO4, filtered andconcentrated. The residue was purified by column chromatography over silica gel.

Reference： [1]Li, Haiwei; Li, Man; Xu, Renyang; Wang, Shouxin; Zhang, Yongmin; Zhang, Lihe; Zhou, Demin; Xiao, Sulong [European Journal of Medicinal Chemistry, 2019, vol. 163, p. 560 - 568]

78
[ 1486-51-7 ]
4-(benzyloxy)benzoyl fluoride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
28%	With (bis-(2-methoxyethyl)amino)sulfur trufluoride In dichloromethane at 0℃; for 0.5h; Schlenk technique; Inert atmosphere;
	Stage #1: p-(benzyloxy)benzoic acid In dichloromethane at 0℃; for 0.5h; Schlenk technique; Stage #2: With (bis-(2-methoxyethyl)amino)sulfur trufluoride In dichloromethane at 0℃; for 0.5h; Schlenk technique;	3.2.2. Representative Procedure for the Synthesis of Acyl Fluorides from Carboxylic Acids General procedure: To a 20 mL of Schlenk tube charged with a magnetic stir bar, were successively added carboxylic acid (3.0 mmol) and CH2Cl2 (15 mL). After the mixture was stirred at 0 °C for 30 min, Deoxo-Fluorreagent (608 L, 3.3 mmol, 1.1 equiv) was slowly added to the reaction mixture. After the reaction mixture was stirred at 0 °C for 30 min, the solution was slowly poured into saturated NaHCO3,extracted with CH2Cl2 (3 15 mL), and dried over MgSO4. The crude product was purified by flash chromatography on silica gel to aord the corresponding acyl fluorides 1 [36].
	With N,N,N',N'-tetramethyl-1,8-diaminonaphthalene; fluoro-N,N,N',N'-tetramethylformamidinium hexafluorophosphate In tetrahydrofuran at 20℃;

Reference： [1]Wang, Zhenhua; Wang, Xiu; Nishihara, Yasushi [Chemical Communications, 2018, vol. 54, # 99, p. 13969 - 13972]
[2]Wang, Xiu; Wang, Zhenhua; Liu, Li; Asanuma, Yuya; Nishihara, Yasushi [Molecules, 2019, vol. 24, # 9]
[3]Malapit, Christian A.; Bour, James R.; Brigham, Conor E.; Sanford, Melanie S. [Nature, 2018, vol. 563, # 7729, p. 100 - 104]

79
[ 1486-51-7 ]
[ 50816-33-6 ]

Yield	Reaction Conditions	Operation in experiment
72%	With dipotassium hydrogenphosphate; [4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine-N1,N1′]bis{3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-κN]phenyl-κC}iridium(III) hexafluorophosphate; 2,4,6-Triisopropylthiophenol; water-d2; triphenylphosphine In dichloromethane at 20℃; for 36h; Inert atmosphere; Irradiation; Schlenk technique; Sealed tube;
72%	With dipotassium hydrogenphosphate; [4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine-N1,N1′]bis{3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-κN]phenyl-κC}iridium(III) hexafluorophosphate; 2,4,6-Triisopropylthiophenol; water-d2; triphenylphosphine In dichloromethane at 20℃; for 36h; Irradiation; Inert atmosphere; Sealed tube;	4 Example 4 Weighed first (45.6 mg, 0.2 mmol), photocatalyst Ir[dF(CF3)ppy]2(dtbbpy)PF6 (2.3mg, 0.002mmol), Κ2ΗΡΟ4 (34.8mg, 1.0equiν.), and Ρh3Ρ (0.22mmol, 57.6mg, 1.1equiv.) was added to the reaction tube, and the gas was exchanged three times through a vacuum line. Under an argon atmosphere, DCM/D2O (2.0 mL, 1: 1 ν/ν) was added. Then, 2,4,6-triisopropylthiophenol (0.03 mmol, 7.1 mg) was carefully added, and then the tube was sealed and placed under a 5W blue LEDs lamp and allowed to react at room temperature for 36 hours. At the end of the reaction. The reaction completed, the mixture was quenched with water, and extracted with DCM (3x10mL). Rotary evaporated organic phase was dried over anhydrous Na2SO4 the solvent was removed by dry-like, column chromatography (300-400 mesh silica gel chromatography) (eluent: petroleum ether - ethyl acetate, volume ratio: 40-10: 1) to give 30.7mg, yield 72%.

Reference： [1]Zhang, Muliang; Yuan, Xiang-Ai; Zhu, Chengjian; Xie, Jin [Angewandte Chemie - International Edition, 2019, vol. 58, # 1, p. 312 - 316][Angew. Chem., 2019, vol. 131, # 1, p. 318 - 322,5]
[2]Current Patent Assignee: NANJING UNIVERSITY - CN109293484, 2019, A Location in patent: Paragraph 0033

80
[ 1486-51-7 ]
[ 52568-28-2 ]
4-(benzyloxy)-N-(2-(pyridin-2-yl)propan-2-yl)benzamide [ No CAS ]

Reference： [1]Organic Letters,2019,vol. 21,p. 2645 - 2649

81
[ 1486-51-7 ]
[ 52568-28-2 ]
4-(benzyloxy)-2,6-dibromo-N-(2-(pyridin-2-yl)propan-2-yl)benzamide [ No CAS ]

Reference： [1]Organic Letters,2019,vol. 21,p. 2645 - 2649

82
[ 1486-51-7 ]
2-piperazin-1-yl-3H-quinazolin-4-one hydrochloride [ No CAS ]
2-[4-(4-phenylmethoxybenzoyl)piperazin-1-yl]-3H-quinazolin-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72.5%	Stage #1: 2-piperazin-1-yl-3H-quinazolin-4-one hydrochloride With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 25℃; for 0.5h; Stage #2: p-(benzyloxy)benzoic acid In N,N-dimethyl-formamide at 20℃; for 16h;	63 method C Example 63 -[4-(4-phenylmethoxybenzoyl)piperazin-l-yl]-3H-quinazolin-4-one To a stirred solution of 2-piperazino-4(3H)-quinazolinone hydrochloride (300 mg, 1.12 mmol, CAS RN 591244-85-8) in DMF (5 mL) was added diPEA (0.6 mL, 3.4 mmol), EDC.HC1 (431.2 mg, 2.3 mmol, CAS RN 25952-53-8), HOBT (304 mg, 2.25 mmol, CAS RN 2592-95-2) at 25°C. After 30 min stirring, 4-benzyloxybenzoic acid (256 mg, 1.12 mmol, CAS RN 1486-51-7) was added and the reaction mixture was stirred at RT for 16 h. 0 (20 mL) was added and the precipitate was collected by filtration and washed with 0 (2 x 10 mL) followed by etOAc (10 mL). The filter cake was dried under high vacuum to afford a white solid (362 mg, 72.5%). H NMR (DMSO-d6, 400 MHz at 100°C): δ ppm 3.61-3.70 (m, 8H), 5.17 (s, 2H), 6.94-7.17 (m, 3H), 7.29-7.47 (m, 8H), 7.57-7.60 (m, 1H), 7.92-7.94 (m, 1H), 11.17 (br s, 1H). MS (ESI): m/z = 440.9 [M+H]+.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2019/72785, 2019, A1 Location in patent: Page/Page column 112

83
[ 92418-38-7 ]
[ 1486-51-7 ]
6-O-(4-benzyloxybenzoyl)-1-O-methyl-D-glucopyranoside [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	Stage #1: p-(benzyloxy)benzoic acid With sodium hydride In N,N-dimethyl-formamide at 0℃; Inert atmosphere; Stage #2: (3,4,5-trihydroxy-6-methoxytetrahydro-2H-pyran-2-yl)methyl 4-methylbenzenesulfonate In N,N-dimethyl-formamide at 80℃; for 16h; Inert atmosphere;	1 General description: General procedure: Sodium hydride (17.22 mg, 430.58 μmol) is added at 0°C under argon atmosphere to a solution of the benzoic acid (430.58 μmol) in N,N-dimethylformamide (5 mL). Subsequently 6-O-(tosyl)-methyl-a-D-glucopyranoside (100 mg, 287.05 μmol) is added and the solution is stirred at 80°C for 16 h. The reaction is monitored by LC/MS. CH2CI2 (25 mL) is added and the organic phase is washed twice with H2O. The organic phase is dried with Na2S04, filtered and evaporated.

Reference： [1]Current Patent Assignee: SANOFI - WO2019/106122, 2019, A1 Location in patent: Page/Page column 44; 57-58

84
[ 1486-51-7 ]
3,4-O-isopropylidene-1-O-methyl-D-galactopyranoside [ No CAS ]
6-O-(4-benzyloxybenzoyl)-3,4-O-isopropylidene-1-O-methyl-D-galactopyranoside [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
79%	With dmap; dicyclohexyl-carbodiimide In dichloromethane; N,N-dimethyl-formamide at 25℃; for 1h;	217.1; 219.1 Step-1 : 6-(4-Benzyloxy-benzoyl)-3,4-O-isopropylidene-methyl-β-D- galactopyranoside To 3,4-O-isopropylidene-methyl-a-D-galactopyranoside (3 g, 12.82 mmol) in CH2CI2/N,N-dimethylformamide (1 :1 ; 60 mL), dicyclohexylcarbodiimide (2.64 g, 12.82 mmol), 4-benzyloxybenzoic acid (2.92 g, 12.82 mmol) and dimethylaminopyridine (312 mg, 2.56 mmol) were added at 25°C and stirred for 1 h. After completion of the reaction, the reaction mixture was filtered and the residue obtained was washed with CH2CI2. The filtrate collected was washed (sat. aqueous NaHCO3followed by H2O). The separated organic layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography (MPLC) eluting with 0-50 % ethyl acetate in n- hexane.Yield: 4.5 g (79 %), white solidLC/MS: m/z = 467.00 [M + Na]+; calculated: 467.49 tR(l = 220 nm): 1.96 min (LC/MS- method E).1H NMR (400 MHz, DMSO-d6) d [ppm] = 7.92 (d, J = 8.80 Hz, 2 H), 7.44 - 7.47 (m, 2 H), 7.33 - 7.42 (m, 3 H), 7.14 (d, J = 8.80 Hz, 2 H), 5.35 (d, J = 4.89 Hz, 1 H), 5.18 (s, 2 H), 4.35 - 4.44 (m, 2 H), 4.19 (d, J = 5.38 Hz, 1 H), 4.15 (dd, J = 4.40, 7.34 Hz, 1 H), 4.10 (d, J = 8.31 Hz, 1 H), 3.98 (t, J = 6.11 Hz, 1 H), 3.34 (s, 3 H), 3.18 - 3.24 (m, 1 H), 1.40 (s, 3 H), 1.26 (s, 3 H).

Reference： [1]Current Patent Assignee: SANOFI - WO2019/106122, 2019, A1 Location in patent: Page/Page column 78-79; 82-84

85
[ 1486-51-7 ]
N-benzyloxycarbonyldezocine [ No CAS ]
C₃₈H₃₉NO₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69.1%	With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20 - 25℃;	52.1 Step 1 A 100 mL round-bottomed flask was loaded with Compound 52.1 (343 mg, 1.503 mmol), Compound 2a (572 mg, 1.507 mmol), DIPEA (585 mg, 4.526 mmol), 10 mL of dichloromethane and HATU (630 mg, 1.657 mmol). The mixture was stirred at room temperature overnight. The reaction was monitored by LC-MS until completion. The reaction solution was concentrated and purified by combiflash (0-15% EA/hexane) to give Compound 52-1 (700 mg, 69.1%) as a colorless oil. MS m/z (ESI): 590.2 [M+H]+

Reference： [1]Current Patent Assignee: YANGTZE RIVER PHARMACEUTICAL GROUP CO LTD - US2019/161468, 2019, A1 Location in patent: Paragraph 0154; 0345; 0346

86
[ 1486-51-7 ]
[ 52805-36-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: thionyl chloride; N,N-dimethyl-formamide / dichloromethane / 12 h / 20 °C / Schlenk technique; Inert atmosphere 2: bis(1,5-cyclooctadiene)nickel ⁽⁰⁾; triphenylphosphine / toluene / 1 h / 110 °C / Schlenk technique; Inert atmosphere
	Multi-step reaction with 2 steps 1.1: 2-chloro-1-methyl-pyridinium iodide; dmap / dichloromethane / 0.08 h 1.2: 16 h / 0 - 20 °C 2.1: anhydrous potassium acetate / 22 h / 120 °C / Inert atmosphere; Sealed tube

Reference： [1]Wang, Zhenhua; Wang, Xiu; Ura, Yasuyuki; Nishihara, Yasushi [Organic Letters, 2019, vol. 21, # 17, p. 6779 - 6784]
[2]Abe, Masahiro; Nitta, Sayasa; Miura, Erina; Kimachi, Tetsutaro; Inamoto, Kiyofumi [Journal of Organic Chemistry, 2022, vol. 87, # 6, p. 4460 - 4467]

87
[ 616224-38-5 ]
[ 1486-51-7 ]
methyl 4-[(4-benzyloxybenzoyl)amino]-3-(methylamino)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	With 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 0 - 20℃; for 15h;	Methyl 4-[(4-benzyloxybenzoyl)amino]-3-(methylamino)benzoate (1-1): Methyl 4-amino-3-(methylamino)benzoate (0.51 g, 2.83 mmol) in DMF (3 ml) was added to a solution of 4-benzyloxybenzoic acid (0.64 g, 2.83 mmol) in DMF (2 ml) at 0 °C. Subsequently, HOAt (0.41 g, 3.1 mmol) and WSCI-HCl (0.59 g, 3.1 mmol) were added to the former solution at 0 °C and stirred at 20 °C for 15 h. The reaction mixture was quenched with sat. NH4Cl and extracted with CH2Cl2. The combined extracts were washed with H2O and brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by the silica gel column chromatography to give 1-1 in 25% yield.

Reference： [1]Fujimori, Ko; Iguchi, Yusuke; Yamashita, Yukiko; Gohda, Keigo; Teno, Naoki [Molecules, 2019, vol. 24, # 22]

88
[ 1486-51-7 ]
[ 66315-16-0 ]
methyl 3-[(4-benzyloxybenzoyl)amino]-4-(methylamino)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	With 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 0 - 20℃; for 15h;	Methyl 3-amino-4-(methylamino)benzoate (0.49 g, 2.75 mmol) in DMF (5 ml) was added to a solution of 4-benzyloxybenzoic acid (0.62 g, 2.75 mmol) in DMF (4 ml) at 0 C. Subsequently, HOAt (0.4 g, 3.0 mmol) and WSCI-HCl (0.58 g, 3.0 mmol) were added to the former solution at 0 C and stirred at 20 C for 15 h. The reaction mixture was quenched with sat. NH4Cl and extracted with CH2Cl2. The combined extracts were washed with H2O and brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by the silica gel column chromatography to give 2-1 in 58% yield.

Reference： [1]Molecules,2019,vol. 24

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	1486-51-7	MDL No. :	MFCD00016527
Formula :	C₁₄H₁₂O₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	AQSCHALQLXXKKC-UHFFFAOYSA-N
M.W :	228.24	Pubchem ID :	73880
Synonyms :

Num. heavy atoms :	17
Num. arom. heavy atoms :	12
Fraction Csp3 :	0.07
Num. rotatable bonds :	4
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	64.38
TPSA :	46.53 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.34 cm/s

Log Po/w (iLOGP) :	2.17
Log Po/w (XLOGP3) :	3.32
Log Po/w (WLOGP) :	2.81
Log Po/w (MLOGP) :	2.8
Log Po/w (SILICOS-IT) :	2.79
Consensus Log Po/w :	2.78

[ CAS No. 1486-51-7 ] {[proInfo.proName]}

Quality Control of [ 1486-51-7 ]

Related Doc. of [ 1486-51-7 ]

Product Details of [ 1486-51-7 ]

Calculated chemistry of [ 1486-51-7 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 1486-51-7 ]

Application In Synthesis of [ 1486-51-7 ]

[ 1486-51-7 ] Synthesis Path-Downstream 1~88

Related Functional Groups of
[ 1486-51-7 ]

Aryls

Ethers

Carboxylic Acids

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.56

Log S (ESOL) :	-3.61
Solubility :	0.0567 mg/ml ; 0.000248 mol/l
Class :	Soluble
Log S (Ali) :	-3.97
Solubility :	0.0243 mg/ml ; 0.000106 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.44
Solubility :	0.00827 mg/ml ; 0.0000362 mol/l
Class :	Moderately soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.6

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H319	Packing Group:	N/A
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling