Name: 2345-34-8|4-Acetoxybenzoic acid|98%
Brand: Ambeed
SKU: A429729
Price: 6.0 USD
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1
[ 2345-34-8 ]
[ 27914-73-4 ]

Yield	Reaction Conditions	Operation in experiment
100%	With oxalyl dichloride at 20℃; for 4h;	2 Step 2 To a clean dried 100 ml two neck round bottom flask was added [99] (2.0 g, 1 1 . 1 mmol) in addition of oxalyl chloride (3.0 ml, 33.3 mmol). The resulting solution was stirred at RT for 4 hrs. After completion of the reaction, excess oxalyl chloride was evaporated on a rotary evaporator under nitrogen atmosphere to yield the corresponding acid chloride as a brown solid (2. 16 g, 100%) [100]. The resulting brown solid was dissolved in DCM (50 ml) and cooled to 0 °C followed by the addition of a 2.0 M solution of dimethyl amine in THF ( 1 1.2 ml, 24.4 mmol) and DIPEA ( 1.33 ml, 12.2 mmol) and stirred it for 3 hrs at RT. The progress of the reaction was monitored by TLC. The solvent was evaporated under reduced pressure and crude was used as such for further step. ESIMS: 208 (M+ + 1 )
100%	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 4h;
100%	With oxalyl dichloride In dichloromethane at 20℃; for 6h;	2.1 Step 1: 4-(chlorocarbonyl)phenyl acetate (Compound 9) />Hydroxybenzoic acid was reacted with acetic anhydride and triethylamine at 100 °C for 6 h to provide 4-acetoxybenzoic acid. After oven drying, 4-acetoxybenzoic acid was mixed with oxalyl chloride in methylene chloride at room temperature for about 6 hours to give 4-(chlorocarbonyl)phenyl acetate in quantitative yield.

99%	With thionyl chloride at 79℃; for 4h; Heating / reflux;	30.1 Example 30; (Formula (1): n=3, A=-Cy-, X=H, Y=H, B=-COO-(E17)); Preparation of (R)-4-(3-ethyl-1-methylpentyloxycarbonyl)phenyl-4-(trans-4-n-propylcyclohexyl)phenylcarboxylate; (1) Synthesis of 4-acetoxybenozic acid chloride 40.0 Grams (222 mmol) of 4-acetoxybenzoic acid and 264 g (2.22 mol) of purified thionyl chloride were placed in a reactor, and the mixture was refluxed under heat (79° C.) for 4 hours. [00130] Then, thionyl chloride was first distilled off under atmospheric pressure, 150 ml of toluene was added, and toluene and thionyl chloride were distilled off under reduced pressure, to give 44 g of 4-acetoxybenzoic acid chloride (yield 99%).
99%	With thionyl chloride In toluene	30.1 (1) (1) Synthesis of 4-acetoxybenozic acid chloride 40.0 Grams (222 mmol) of 4-acetoxybenzoic acid and 264 g (2.22 mol) of purified thionyl chloride were placed in a reactor, and the mixture was refluxed under heat (79°C) for 4 hours. Then, thionyl chloride was first distilled off under atmospheric pressure, 150 ml of toluene was added, and toluene and thionyl chloride were distilled off under reduced pressure, to give 44 g of 4-acetoxybenzoic acid chloride (yield 99 %).
98%	With thionyl chloride In N,N-dimethyl-formamide at 80℃; for 3h; Inert atmosphere;	1-1 [Example 1-1] Synthesis of diamine (12) Into a three-necked flask, 36.62 g (200 mmol, manufactured by Tokyo Kasei Kogyo Co., Ltd.) of 4-acetoxybenzoic acid and an appropriate amount of thionyl chloride were added, and a few drops of DMF was added as a catalyst, and the mixture was refluxed at 80° C for 3 hours in a nitrogen atmosphere.After the reaction, benzene was added in an appropriate amount, and thionyl chloride was azeotropically distilled off under reduced pressure, followed by vacuum drying at 30° C. for 12 hours to obtain a chlorinated compound represented by the formula (7) as a colorless liquid (yield: 98%).
92%	With thionyl chloride for 3.5h; Heating / reflux;	5.1 5.1 Synthesis of 4-(chlorocarbonyl)phenyl acetate (510) Thionyl chloride (11.1 mL, 15.3 mmol) was added to 4-acetoxybenzoic acid (2.50 g, 13.9 mmol), and the reaction was warmed to reflux. The reaction was cooled after heating for 3.5 hours, and concentrated in vacuo to give a colorless oil. Toluene was added to the residue and the mixture was concentrated in vacuo to remove any residual thionyl chloride. This process was repeated twice more to give 510 (2.54 g, 92%) as a colorless oil. This material was used in the next step without additional purification. Data for 510: 1H-NMR (400 MHz, CDCl3) δ 8.18 (d, J=8.9 Hz, 2 H), 7.29 (d, J=8.9 Hz, 2 H), 2.36 (s, 3 H) ppm.
92%	With thionyl chloride for 3.5h; Reflux;	1.5.2.1 Thionyl chloride (11.1 mL, 15.3 mmol) was added to 4-acetoxybenzoic acid (2.50 g, 13.9 mmol), and the reaction was warmed to reflux. The reaction was cooled after heating for 3.5 hours, and concentrated in vacuo to give a colorless oil. Toluene was added to the residue and the mixture was concentrated in vacuo to remove any residual thionyl chloride. This process was repeated twice more to give 510 (2.54 g, 92%) as a colorless oil. This material was used in the next step without additional purification.Data for 510: 1H-NMR (400 MHz, CDCl3) δ 8.18 (d, J=8.9 Hz, 2H), 7.29 (d, J=8.9 Hz, 2H), 2.36 (s, 3H) ppm.
90%	With thionyl chloride for 4h; Heating / reflux;	3.1 Example 3; (General formula (1): n = 5, X = -Ph-Ph-COO-Ph- (E3)), Preparation of 4-((R)-1-methyl-3-ethylpentyloxycarbonyl)phenyl-4'-((R)-1-methylhexyloxycarbonyl)biphenyl-4-carboxylate; (1) Synthesis of 4-acetoxybenzoyl chloride 100 g (0.555 mol) of 4-acetoxybenzoic acid was added to 400 g (3.36 mol) of thionyl chloride, and a mixture was refluxed under heat for 4 hours. Then, excess thionyl chloride was distilled off, and a remainder was purified by distillation under reduced pressure (4 mmHg, 116°C), to give 99 g (0.498 mol, yield 90 %) of an end compound.
90%	With thionyl chloride for 8h; Reflux;	4-Acetoxy benzoyl chloride Into a single necked 100 mL round bottom flask,equipped with reflux condenser, 4-acetoxy benzoicacid (9.00 g, 0.05 mol) was placed. To this flask,thionyl chloride (5 mL, 0.07 mol) was added dropwiseand the reaction mixture refluxed for 8 hr. Theinitial heterogeneous mass was homogenized. Excessthionyl chloride was removed by distillation. Thecrude product was purified by distillation underreduced pressure at 130°C. Yield: 90%; m.p. 29-30°Cand b.p. 132°C; IR (Nujol): 1780 (COCl), 1730 (C=Ostretching) and 1370 cm-1 (-CH, bending); 1H NMR(CDCl3): d 2.1 (s, 3H), 7.1 (d, 2H) and 8.0 (d, 2H).
90%	With thionyl chloride for 8h; Reflux;	2.2b 4-Acetoxy benzoyl chloride: 4-Acetoxy benzoicacid (9.0 g, 0.05 mole) was placed in a single necked 100 mLround bottom flask. To this flask, thionyl chloride (5mL, 0.07mole) was added drop wise and refluxed the reaction mixturegently for 8 h. The initial heterogeneous mass was homogenized.Excess thionyl chloride was removed by distillation.The crude acid chloride was purified by double distillationunder reduced pressure. Yield: 90%. M.p.: 29°C. IR (Nujol,cm-1): 1780 (COCl), 1730 (C=O stretching).
80%	With thionyl chloride for 2.5h; Heating;
79%	With thionyl chloride In dichloromethane at 40℃; for 10h;
75%	With thionyl chloride In toluene for 3h; Reflux;
75%	With thionyl chloride In toluene for 3h; Reflux;
71%	With phosphorus pentachloride In diethyl ether at 20℃; for 2h;
	With tetrachloromethane; phosphorus pentachloride
	With thionyl chloride
	With thionyl chloride for 3h; Heating;
	With thionyl chloride In chloroform for 2h; Heating;
	With thionyl chloride for 0.5h; Heating;
	With thionyl chloride In benzene Heating;
	With thionyl chloride at 60℃; for 6h;
	With thionyl chloride In 1,2-dichloro-ethane; acetone
	With tetrachloromethane; triphenylphosphine In acetonitrile for 0.333333h;
	With thionyl chloride for 3h; Heating;
	With thionyl chloride In tetrahydrofuran
	With thionyl chloride In chloroform Heating;
	With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃; for 2h;
	With thionyl chloride In dichloromethane at 20℃;
	With oxalyl dichloride In chloroform at 20℃; for 4h;
	With thionyl chloride
	With thionyl chloride; N,N-dimethyl-formamide at 50℃; for 5h;
	With thionyl chloride; N,N-dimethyl-formamide at 70℃; for 5h;
	With pyridine; thionyl chloride In N,N-dimethyl-formamide
	With thionyl chloride
	With oxalyl dichloride In DMF (N,N-dimethyl-formamide) for 3h;	7 Reference example 7; 1-(4-acetoxybenzoyl)-2-methyl-1H-indol-4-yl acetic acid benzyl ester Reference example 7 1-(4-acetoxybenzoyl)-2-methyl-1H-indol-4-yl acetic acid benzyl ester Under argon gas, a mixture of 4-acetoxybenzoic acid (516mg), oxalylchloride (0.5ml), and N, N-dimethylformamide (5μl) was stirred for 3 hours.. The mixture was concentrated by vacuum concentration and 4-acetoxybenzoic acid chloride was prepared.. sodium hydroxide (286mg) and tetrabutylammonium chloride (20mg) were added to dichloromethane (7ml) solution containing the compound (400mg) prepared according to reference example 6 at room temperature over stir.. dichloromethane (3ml) solution containing 4-acetoxybenzoic acid chloride prepared by the described above was added to the mixture, which was stirred at room temperature for 1 hour.. The reaction mixture was filtered and the filtrate was concentrated, and the residue was purified by silica gel column chromatography (hexane: ethyl acetate=7:3) to give a title compound (500mg) having the following physical properties. TLC: Rf 0.34 (hexane: ethyl acetate=7:3) NMR (CDCl3): δ 7.76 (d, J = 8.7 Hz, 2H), 7.40-7.20 (m, 7H), 7.08-6.92 (m, 3H), 6.47 (s, 1H), 5.15 (s, 2H), 3.88 (s, 2H), 2.40 (s, 3H), 2.35 (s, 3H).
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 1.5h; Heating / reflux;	42 To a suspension of 4-(acetyloxy)benzoic acid (17) (10.0 g, 55.5 mmol) in dichloromethane (200 ml) oxalyl chloride (15 ml, 172 mmol) and dimethylformamide (0.1 ml) were added. The reaction mixture was stirred at ambient temperature for 30 minutes and at reflux temperature for 1 hour. The volatiles were evaporated in vacuo, the residue was dissolved in benzene (100 ml) and the solvent was evaporated again. The procedure was repeated several times until the poignant smell disappeared after drying in vacuo. The viscous oil was dissolved in tetrahydrofuran (100 ml) and this solution slowly over 10 minutes was added to a prearranged mixture consisting of saturated NaHCO3 solution (100 ml), solid NaHCO3 (11 g), O-benzylhydroxylamine hydrochloride (9.90 g, 62 mmol), and tetrahydrofuran (150 ml). The resulting mixture was stirred at ambient temperature for 1 hour and the volume of the reaction mixture was decreased ca. twice by evaporating the mixture on vacuum rotary evaporator. The residue was extracted with ethyl acetate (3 x 100 ml), the combined organic extracts were successively washed with 2N HCl (100 ml), water (100 ml), brine (100 ml), and dried (Na2SO4). The solvents were evaporated and the residue was crystallized from toluene to give the title compound (14.275 g, 90%) as white crystals, m. p. 120-122°C. 1H NMR (CDCl3, HMDSO) δ: 2.30 (3H, s); 5.02 (2H, s); 7.14 (2H, d, J=8.6 Hz); 7.26-7. 54 (5H, m); 7.69 (2H, d, J=8.6 Hz); 8.56 (1 H, br s).
99 g (0.498 mol. yield 90%)	With thionyl chloride	4.1 (1) (1) Synthesis of 4-acetoxybenzoyl chloride 100 Grams (0.555 mol) of 4-acetoxybenzoic acid was added to 400 g (3.36 mol) of thionyl chloride, and the mixture was refluxed under heat for 4 hours. Then, excess thionyl chloride was distilled off, and then the remainder was purified by distillation under reduced pressure (4 mmHg, 116° C.), to give 99 g (0.498 mol. yield 90%) of an end compound.
	With oxalyl dichloride In chloroform at 20℃; for 1h;	1.4 Step 4: Production of 4-acetoxybenzoyl chloride To a solution of 4-acetoxybenzoic acid (1.96 g, 10.9 mmol) in chloroform (40 ml) was added oxalyl dichloride (1.42 ml, 16.3 mmol), a catalytic amount of N,N-dimethylformamide was added dropwise, and the mixture was stirred at room temperature for 1 hr. The solvent was evaporated under reduced pressure to give 4-acetoxybenzoyl chloride as a crude product. The obtained crude product was used for Step 6 without further purification.
	With thionyl chloride In N,N-dimethyl-formamide; benzene	4.i Step i) STR77 Step i) STR77 In a 20 ml-round-bottomed flask, 2.90 g (16.1 mM) of 4-acetoxybenzoic acid and 3.7 ml of thionyl chloride were placed. To the mixture, two drops of N,N-dimethylformamide was added at room temperature under stirring, followed by heat-refluxing for 20 minutes under stirring. After the reaction, dry benzene was added to the reaction mixture, followed by distilling-off of excessive thionyl chloride together with benzene. The above operation was repeated two times to obtain 4-acetoxybenzoic acid chloride.
	With phosphorus pentachloride In benzene	43.ii Step ii) STR219 Step ii) STR219 In a 200 ml-reaction vessel, 21.4 g (1.1810-1 M) of p-acetoxybenzoic acid and 80 ml of dry benzene were placed. To the mixture, 25.0 g (1.2010-1 M) of phosphorus pentachloride was added in 10 minutes at room temperature, followed by stirring for 3 hours at 50° C. After cooling, the solvent of the reaction mixture was distilled off to provide oily p-acetoxybenzoyl chloride.
	With thionyl chloride	58 5-(4-Acetoxyphenyl)carboxyamido-6-amino-3-methyl-1-phenyluracil The obtained 4-acetoxybenzoic acid was reacted with SOCl2 to prepare 4-acetoxybenzoyl chloride.
	With thionyl chloride	1.1.2 2) After heating and refluxing 1.4 g (8.0 mmol) of 4-acetoxybenzoic acid and 6 ml of thionyl chloride, surplus thionyl chloride was removed, and 4-acetoxybenzoic acid chloride was obtained.
	With phosphorus pentachloride In benzene	14 p-dodecyloxybenzoic acid-p'-thiocarboxylic acid phenyl-S-p"-(2-methylbutyloxy)phenyl STR28 P-acetyloxybenzoic acid (5.5610-2 mol) was dissolved in 45 ml of benzene, and 11.8 g (5.5610-2 mol) of PCl5 was added in 6 fractions at an interval of 5 minutes each at room temperature. Then, the mixture was stirred for 20 minutes at room temperature, followed by heat-refluxing under stirring for 5 hours. After distilling off the solvent, 12.7 g of p-acetyloxybenzoic acid chloride was obtained as a pale yellow oily product.
	With phosphorus pentachloride In benzene	12 Production of 4-(3-pentyloxybutoxycarbonyl)phenol. Example 12 Production of 4-(3-pentyloxybutoxycarbonyl)phenol. 10 g of p-acetyloxybenzoic acid was added to 45 ml of benzene, and 11.8 g of PCl5 was added little by little under stirring at room temperature. After 8.5 hours of heat-refluxing thereafter, the solvent was distilled off to obtain 11.5 g of p-acetyloxybenzoic acid chloride.
	With thionyl chloride at 80℃; for 0.5h;
	With thionyl chloride at 80℃; for 5h;
	With thionyl chloride In chlorobenzene at 80℃; for 1.5h;	10.1 Example 10 [00349] Step 1 [00350] Acetic acid 4-chlorocarbonyl-phenyl ester. A solution of 4-acetoxybenzoic acid (200 mg, 1.11 mmol), thionyl chloride(1.6 mL), 1 drop of DMF, and 7.5 mL of chlorobenzene was heated to 80° C. for 1.5 hrs. The reaction was then cooled to room temperature and the solvent and excess thionyl chloride were removed in vacuo. Theoretical yield of the title compound was assumed and the residue was used as is. [00351] Step 2 [00352] Methanesulfonic acid 4-[3-(4-hydroxy-benzoyl)-6-methanesulfonyloxy -benzo[b]thiophen-2-yl]-phenyl ester. To a solution of methanesulfonic acid 4-(6-methanesulfonyloxy-benzo[b]thiophen-2-yl)-phenyl ester1(200 mg, 0.5 mmol) in 14 mL of methylene chloride was added the product from Step 1, Example 10 (104 mg, 0.53 mmol) and triflic acid (0.47 mL, 5.3 mmol). The reaction was stirred at reflux for 16 hrs, cooled to room temperature, and poured into saturated sodium bicarbonate solution and was extracted into methylene chloride. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography using 20% Ethyl acetate/ Hexanes to 50% Ethyl acetate/Hexanes as the gradient eluant to obtain 125 mg of the title compound. [00353] Step 3 [00354] Methanesulfonic acid 4-{6-methanesulfonloxy-3-[4-(1-methyl-piperidin-2-ylmethoxy)-benzoyl]-benzo[b]thiophen-2-yl}-phenyl ester. A solution of the product from Step 2, Example 10 (115 mg, 0.22 mmol), (1-methyl-piperidin-2-yl)-methanol (28.7 mg, 0.22 mmol), and triphenylphosphine (75 mg, 0.29 mmol) in 3 mL of THF was cooled to 0° C. and diethyl azodicarboxylate (0.051 mL, 0.26 mmol) was added dropwise. After the addition was complete, the reaction was allowed to warm to room temperature and was stirred for 16 hrs. The THF was evaporated off and the residue was chromatographed on silica gel using 1% MeOH-1% Diethylamine-methylene chloride as the eluant to give 80 mg of the title compound. [00355] Step 4 [00356] [6-Hydroxy-2-(4-hydroxy-phenyl)-benzo[b]thiophen-3-yl]-[4-(1-methyl -piperidin-3-ylmethoxy)-phenyl]-methanone. A solution of the product from Step 3, Example 10 (80 mg, 0.13 mmol) and 0.25 mL of 5N NaOH in 8 ml of ethanol was heated to reflux for 1 hr. The solvent was evaporated and the residue was diluted with water. The reaction was acidified with 3N HCl then made basic with saturated sodium bicarbonate solution. This aqueous solution was extracted with 1:2 MeOH/ methylene chloride. The combined organic layers were dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude product was chromatographed on silica gel using 5% MeOH/CHCl3 to 10% MeOH/CHCl3 as the gradient eluant to obtain the title compound. [00357] 1H NMR (MeOH-d4) δ7.70(d, 2H), 7.40(d, 1H), 7.25(d, 1H), 7.15(d, 2H), 6.85(m, 3H), 6.60(d, 2H), 4.05(m, 2H), 2.95(m, 1H), 2.35(s, 3H), 2.30(m, 2H), 1.65(m, 6H).Example 11
	With oxalyl dichloride In dichloromethane at 0 - 20℃;	35.a To a suspension of acetoxybenzoic acid (350 mg, 1.97 mmol) in CH2Cl2 (36 mL) was added oxalyl chloride (0.696 mL, 7.95 mmol) and catalytic amount of DMF at 0° C., and the mixture was stirred for 5 hr at rt. The solvent was evaporated, and the residual oxalyl chloride was removed with azeotropic distillation using toluene under nitrogen atmosphere. The resulting acid chloride was added to a solution of 5-amino-2-(4-methoxyphenylamino)thiazole-4-carboxamide (350 mg, 1.32 mmol) in pyridine (10 mL) at 0° C., and the mixture was stirred for 2 hr at rt. The reaction mixture was quenched by adding of ice-water, and extracted with EtOAc. The organic layer was washed with water twice, dried over Na2SO4 and concentrated. The residue was triturated with 50% EtOAc in Et2O, and the resulting solids were collected by filtration and washed with 50% EtOAc in Et2O to afford the titled compound (382 mg, 68% yield).1H-NMR (400 MHz, DMSO-d6) δ (ppm) 2.32 (s, 3H), 3.73 (s, 3H), 6.89 (d, 2H, J=8.8 Hz), 7.39 (d, 2H, J=8.8 Hz), 7.6-7.7 (m, 3H), 7.84 (br, 1H), 7.94 (d, 2H, J=8.8 Hz), 9.90 (s, 1H), 12.59 (s, 1H).
	With oxalyl dichloride In dichloromethane at 0 - 20℃;	97 A solution of 4-acetoxy-benzoic acid acid (108 mg, 0.598 mmoL) in CH2CI2 (5 ml_) was treated with (COCI)2 (0.07 mL, 0.796 mmoL) and 1 drop, a catalytic amount, of DMF at 0°C. The reaction mixture was slowly warmed to room temperature. The CH2CI2 was removed and dried in vacuo. The 4- acetoxy-benzoic acyl chloride in THF (2 mL) was treated with the indole- 8- Methoxy-6,11-dihydro-5-oxa-11-aza-benzo[a]fluorene (100 mg, 0.398 mmoL) followed by Et3N (0.796 mmoL, 0.11 mL) at 0°C. The reaction was slowly warmed to room temperature over 2 hours. THF was removed in vacuo. The residue was partitioned between CH2CI2 and saturated NaHCO3. The aqueous phase was extracted two times with CH2CI2. The organic layers from the two extractions were combined, washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated to yield a brown oil. The crude material (the oil) was then purified by column chromatography (silica gel, hexanes: EtOAc 4:1 as eluent) to yield the title compound as a pale solid. 1H NMR (CDCI3) δ 8.02 ~ 6.75 (m, 11 H), 5.52 (s, 2H), 3.98 (s, 3H), 2.55(s, 3H).MS (m/z): MH+, 414.
	With oxalyl dichloride In dichloromethane at 0 - 20℃;	97 A solution of 4-acetoxy-benzoic acid acid (108 mg, 0.598 mmoL) in CH2CI2 (5 ml_) was treated with (COCI)2 (0.07 ml_, 0.796 mmoL) and 1 drop, a catalytic amount, of DMF at 0°C. The reaction mixture was slowly warmed to room temperature. The CH2CI2 was removed and dried in vacuo. The 4- acetoxy-benzoic acyl chloride in THF (2 ml_) was treated with the indole- 8- Methoxy-6,11-dihydro-5-oxa-11 -aza-benzo[a]fluorene (100 mg, 0.398 mmoL) followed by Et3N (0.796 mmoL, 0.11 ml_) at 0°C. The reaction was slowly warmed to room temperature over 2 hours. THF was removed in vacuo. The residue was partitioned between CH2CI2 and saturated NaHCO3. The aqueous phase was extracted two times with CH2CI2. The organic layers from the two extractions were combined, washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated to yield a brown oil. The crude material (the oil) was then purified by column chromatography (silica gel, hexanes: EtOAc 4:1 as eluent) to yield the title compound as a pale solid. 1H NMR (CDCI3) δ 8.02 ~ 6.75 (m, 11 H), 5.52 (s, 2H), 3.98 (s, 3H), 2.55(s, 3H).MS (m/z): MH+, 414.
	With oxalyl dichloride In dichloromethane at 0 - 20℃;	2.A A slurry of 4-acetoxybenzoic acid (100 g, 555.1 mmol) in CH2Cl2 (50 mL) was treated with a catalytic amount of DMF (0.5 mL) and cooled in ice bath. The reaction was stirred as neat oxalyl chloride (51 mL, 582.82 mmol, 1.05 equiv.) was added dropwise. The reaction was allowed to warm to ambient temperature and stirred overnight. The reaction mixture was concentrated under reduced pressure to give 4-(chlorocarbonyl)phenyl acetate (110 g, 100% th.; 110% pract.), which was used in the next step without further purification; 1H NMR (CDCl3) δ 8.09 (d, 2H), 7.20 (d, 2H), 2.28 (s, 3H) ppm.
	With thionyl chloride Reflux;	5.1.5. General procedures for benzoyl chloride (6a-6m) General procedure: The selected acid was refluxed in thionyl chloride for 2-3 h, and then the solution was cooled to room temperature, and the remaining thionyl chloride was evaporated to afford the acyl chloride, which was used without further purification.
	With thionyl chloride In N,N-dimethyl-formamide at 80℃; for 1h; Inert atmosphere;
	With oxalyl dichloride In toluene for 3h; Reflux; Inert atmosphere;
	With thionyl chloride Reflux;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 8h; Inert atmosphere;
	With thionyl chloride for 2h; Reflux;	General Procedure: The carboxylic acid (1equiv) was refluxed with excess of thionyl chloride for 2 h. The excess of thionyl chloride was evaporated at reduce pressure. The residue was dissolved in toluene (5 mL) and evaporated at reduce pressure until dryness two times. The crude acid chloride was dissolved in acetone. This solution was treated at 0 °C with (+)-6-aminopenicillanic acid (6-APA, 1.5 equiv) dissolved into a 2% NaHCO3/water solution (50 ml), diluted with acetone (40 ml). After stirring at room temperature for 2-4 h, the reaction mixture was washed with ethyl acetate (25 ml). The aqueous layer was poured into ethyl acetate (50 ml) and acidified with a 0.1M HCl/water solution to pH 2-3. The organic phase was washed three times with water and dried with anhydrous Na2SO4. The organic layer was concentrated by evaporating the solvent at reduced pressure and triturated with petroleum ether and ethyl acetate or dichloromethane to give the title compounds.
	With thionyl chloride; N,N-dimethyl-formamide for 0.5h; Inert atmosphere;
	With oxalyl dichloride; N,N-dimethyl-formamide at 20℃; for 1h;
	With thionyl chloride In tetrahydrofuran
	With thionyl chloride
	With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 1h; Inert atmosphere;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0℃;
	With thionyl chloride for 8h; Reflux;
	With thionyl chloride In benzene for 2h; Reflux;
	With thionyl chloride for 3h; Reflux;
	With thionyl chloride; N,N-dimethyl-formamide
	With oxalyl dichloride In dichloromethane at 20℃;
	With thionyl chloride at 81.84℃; for 5h;
	With oxalyl dichloride; N,N-dimethyl-formamide In acetonitrile at 20℃; for 1h;	33 Preparation of 4-(4-(trifluoromethyl)pyridin-2-ylcarbamoyl)phenyl acetate (500-2) To a suspension of 4-acetoxybenzoic acid (500-1) (1.6 g, 8.9 mmol) in anhydrous acetonitrile (10 mL) was added 1 drop of DMF before introducing (COCF)2 (2 mL, 21 mmol). The resulting mixture was stirred at room temperature for 1 hr. The solvent was evaporated. The freshly generated acid chloride was dissolved in anhydrous DCM (3 mL) and the solution was introduced to a solution of 4- (trifluoromethyl)pyridin-2-amine (700 mg, 4.3 mmol) in DCM (3 mL). The reaction mixture was stirred at room temperature for 1 hr before being quenched with MeOH (5 mL). Solvents were removed and the residue was purified by column chromatography (silica gel, 0 to 30% ethyl acetate in petroleum ether) to give 4-(4-(trifluoromethyl)pyridin-2-ylcarbamoyl)phenyl acetate (500-2) (697 mg, 50%) as a solid. LC- MS (ESI): mlz (M+l) 325.2.
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 3h; Inert atmosphere;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane	1 10086] 40 g of 4-acetoxybenzoic acid (222 mmol) was added to a 500 ml round bottom flask and was then dissolved in methylene chloride. Subsequently, 31 g of oxalyl chloride (244 mmol) and ito 5 drops of DMF were added thereto and then reacted for 3 hours or more. Reaction termination was confirmed using thin layer chromatography (TLC). When the reaction was finished, a material, in which a hydroxyl group of 4-acetoxybenzoic acid was chlorinated, was obtained by evaporation.
88.1 g	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃;	1.1 (1) Preparation of 4-acetoxy-benzoyl chloride 4-acetoxy-benzoic acid 80g, and then the turbid solution made by diluting 2.2 eq. In methylene chloride (MC) solvent was added as a catalyst in dimethylformamide was stirred at room temperature for 1 to 3 drops. Chloride at room temperature 58.92g, 2.3 eq oxalyl while stirring Slowly added in and stirred for a few hours; To remove residual oxalyl chloride and the methylene chloride solvent through a rotary evaporator under reduced pressure acetone was synthesized 4-benzoyl chloride 88.1g of the liquid phase.
	With thionyl chloride at 80℃; for 5h;
	With thionyl chloride In N,N-dimethyl-formamide; toluene at 60℃; for 2h; Inert atmosphere;	1 225 g of toluene, three drops of DMF, and 90.0 g of p-acetoxybenzoic acid (AcPOB) were put into 1000 ml four mouth flask purged with nitrogen, and dssolved by stirring. Subsequently, 89.2 g of thionyl chloride was added and stirred at 60 degrees C for 120 minutes, and toluene was distilled off under reduced pressire to obtain p-acetoxybenzoyl chloride. 68 ml of allyl alcohol previously dissolved in 100 ml of N-methyl-2-pyrrolidone was added dropwise to this p-acetoxybenzoyl chloride at 0 degree C and stirred at room temperature for 1 hour. The reaction mixture was transferred to the separating funnel containing ethyl acetate. A saturated sodium bicarbonate aqueous solution was added to this reaction mixture and the mixture was separated. Further, a saturation sodium chloride aqueous solution was added and the liquids were separated. The unreacted carboxylic acid, the raw material, and the inorganic component were removed by discarding the aqueous layer. Sodium sulfate was added to the obtained ethyl acetate layer, dehydrated by stirring, filtered and the filtrate was concentrated under reduced pressure to obtain 107.2 g of yellow liquid.
88.1 g	With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide	1 (1) Preparation of 4-acetoxybenzoyl chloride 72.72 g of 4-acetoxybenzoic acid, 2 equivalents, was diluted in methylene chloride (MC) solvent to make a cloudy solution, and then dimethylformamide 1 to 3 drops were added as a catalyst and stirred at room temperature. At the same time as stirring, 51.23 g of oxalyl chloride, 2 equivalents, And the mixture was stirred for 1 to 2 hours. The residual oxalyl chloride and methylene chloride The rye solvent was removed to obtain 88.1 g of liquid 4-acetone benzoyl chloride
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 2h;
88.1 g	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃;	1.1 (1) Preparation of 4-acetoxybenzoyl chloride The mixture was diluted with a solvent to prepare a cloudy solution. One to three drops of dimethylformamide were added thereto as a catalyst, and the mixture was stirred at room temperature.Simultaneously with stirring, 58.92 g of oxalyl chloride,2.3 equivalents were added slowly at room temperature and stirred for 1-2 hours.The residual oxalyl chloride and methylene chloride solvent were removed through a rotary evaporator to obtain a liquid88.1 g of 4-acetone benzoyl chloride was synthesized.
	With thionyl chloride at 80℃; for 5h;	2.2. General Procedure for Sulfonamide Derivatives General procedure: Secondary sulfonamides were synthesized using naturally available 4-hydroxy and3,4,5-trihydroxy benzoic acids (gallic acid) in various plants and fruits, which were reacted with aceticanhydride to obtain 4-acetoxy and 3,4,5-triacetoxy benzoic acids for the protection of hydroxyl groups.Then, they were converted to their corresponding chloride derivatives by treating with thionyl chlorideto produce benzoyl chlorides, which underwent reactions with secondary sulfonamides having thiazole, pyrimidine, pyridine, isoxazole and thiadiazole groups to obtain secondary sulfonamidederivatives of acetoxybenzamides and triacetoxybenzamides as one part of target compounds.Deacetylation under acidic conditions gave the other part of our targeted sulfonamide derivatives [28].The reaction scheme is given in Figure 1.
	With thionyl chloride In N,N-dimethyl-formamide for 4h; Reflux;
	With thionyl chloride In dichloromethane Reflux;
	With thionyl chloride at 60℃; for 5h; Inert atmosphere;	1-3 (Example 1-3) Preparation of a compound represented by the formula (C-2B) Under a nitrogen atmosphere, 10.0 g of a compound represented by the formula (C-2B-2)50 mL of thionyl chloride was added and the mixture was heated and stirred at 60 ° C. for 5 hours.Thionyl chloride was distilled off to obtain an acid chloride of the compound represented by the formula (C-2B-2).Under a nitrogen atmosphere, 6.9 g of the compound represented by the formula (C-2B-1), 60 mL of dichloromethane and 5.3 g of pyridine were added to the reaction vessel.A solution of the acid chloride of the compound represented by the formula (C-2B-2) dissolved in 20 mL of dichloromethane was added dropwise while cooling with ice, and the mixture was stirred at room temperature for 5 hours.The reaction solution was washed with 5% hydrochloric acid, water and brine.By distilling off the solvent and drying, 15.1 g of a compound represented by the formula (C-2B-3) was obtained.
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 3h; Inert atmosphere; Reflux;
	With thionyl chloride at 80℃; for 1h;
	With thionyl chloride	6.b (b) (b) 4-Hydroxy-[2-(endobicyclo[3.1.0]hex-6-yl)ethyl]phenyl urea A solution (20 ml.) of thionyl chloride containing 3.0 g of 4-acetoxybenzoic acid (Preparation 5) is refluxed for 3 hours. After evaporation of excess thionyl chloride, 4-acetoxybenzoyl chloride is obtained and dissolved in 15 ml. THF and 15 ml. acetone at 5°.
	With phosphorus pentachloride
	With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃; for 1h; Inert atmosphere;
	With phosgene
	With thionyl chloride In tetrahydrofuran for 2h; Inert atmosphere; Reflux;	1 Reference Example 1 (Synthesis of 4-hydroxybenzoic acid methallyl ester) mixer,90.1 g (0.5 mol) of 4-acetoxybenzoic acid in a 1000 mL four-necked flask equipped with a temperature sensor and a reflux condenser,65.4 g (0.55 mol) of thionyl chloride and 360.3 g of tetrahydrofuran were added, and under nitrogen stream,The temperature was raised to reflux while stirring,The mixture was stirred at the same temperature for 2 hours. Then,After cooling down to 18 ° CEvaporate the solvent by reduced pressure,A liquid of 4-acetoxybenzoic acid chloride was obtained.
	With thionyl chloride; N,N-dimethyl-formamide In chloroform at 30 - 40℃; for 48h;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 22℃; for 2h; Inert atmosphere;	2.a a) [4- [ [4- [4- (2-Pyridyl)piperazin- 1 - yl] phenyl] carb amoyl] phenyl] acetate 4-Acetoxybenzoic acid (1.59 g, 8.8 mmol) was dissolved at 22 °C in DCM (65 ml) un der an inert atmosphere. Oxalyl chloride (1.68 g, 1.16 ml, 13.2 mmol) was added at 22 °C followed by DMF (32.2 mg, 34.1 m, 440 m mol) and the reaction mixture was stirred at 22 °C for 2 h. The mixture was evaporated at 40 °C and the resulting acid chloride was dissolved in DCM (32.3 ml) and added dropwise (5 min) at 22 °C to a solution of 4-(4-(pyridin-2-yl)pi- perazin-l-yl)aniline (Intermediate l.b) (2.24 g, 8.8 mmol) and DIPEA(4.55 g, 6.15 ml, 35.2 mmol) in DCM (80 ml) keeping the internal temperature below 20 °C (ice-bath). Stirring was continued at 22 °C for 30 min. The reaction was stopped by adding at 22 °C MeOH (5.64 g, 7.12 ml, 176 mmol). Stirring was continued for 1 h before filtering through a membrane-fil ter. Solids were washed with DCM (2 x 35 ml) and the cake was dried for 2 min (air dried by suction). Then the cake was washed with H20 (2 x 35 ml) and dried in HV to give the title compound (3.20 g, 87%) as white solid. LC-MS: m/z = 417.3 [M+H]+.
	With thionyl chloride at 80℃; for 1h; Inert atmosphere;	30 The mixture of compound 26.1 (216 mg, 1 .2 mmol, 1.0 eq) in thionyl chloride (2 iiiL) was stirred at 80 °C for 1 h under nitrogen atmosphere. The reaction was monitored by TLC. Then the mixture was quenched with methanol. The residue was dried over sodium sulfate and concentrated under reduced pressure to obtain compound 26.2 (245 mg, crude) as a light yellow oil, which was used directly in the next step without further purification
	With thionyl chloride at 78℃; for 4h;	5.1.4. General procedure for the synthesis of compounds 5a-c, 7a General procedure: 3,4,5-triacetoxybenzoic acid 4a (2000 mg, 6.756 mmol) wasdissolved in SOCl2 (8000 mg, 67.244 mmol). The solution was thenheated under reflux at 78 °C for 4 h. The solvent was removed usinga rotary evaporator under reduced pressure to yield white solid.Yielding 99% compound 5a (2100 mg) as a white solid. Compounds5b-c and 7a were synthesized following the procedure of preparation5a.
	With thionyl chloride for 3h; Reflux;
	With oxalyl dichloride
	With thionyl chloride In dichloromethane at 20℃; for 2h;	To a solution of 4-acetoxybenzoic acid (1.0 g, 5.6 mmol) in driedDCM (10 mL), thionyl chloride (660 mg, 5.6 mmol) was added dropwise,and the reaction mixture was stirred for 2 h at room temperature.After completion of the reaction, the mixture was concentrated undervacuo to give 4-(chlorocarbonyl)phenyl acetate (4), which was usedfurther without purification.
	With thionyl chloride; N,N-dimethyl-formamide at 85℃; for 3h;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 1h; Inert atmosphere;	1 4-(6-Methoxy-2-(4-methoxyphenyl)benzo[b]thiophene-3-carbonyl)phenyl acetate (0309) (50) Oxalyl chloride (9.70 mL, 120 mmol, 3.0 eq) was added dropwise under N2 to a solution of 4-acetoxybenzoic acid (49) (7.206 g, 40 mmol, 1.0 eq) in anhydrous DCM (80 mL) at 0 °C. Then several drops of DMF were added. The solution was warmed to rt and stirred for 1 h. The solution was concentrated and dried to obtain the acyl chloride as a white solid. This intermediate was dissolved in anhydrous DCM (150 mL), then 6- methoxy-2-(4-methoxyphenyl)- benzo[b]thiophene (8.65 g, 32 mmol, 0.8 eq) was added followed by addition of AICI3 (8.00 g, 60 mmol, 1.5 eq) in three portions over a period of 5 min with vigorous stirring at 0 °C under N2. The mixture was warmed to rt and stirred for lh. The reaction was quenched by slow addition of ice-ILO followed by IN HC1 (aq). The layers were separated and the aqueous layer was extracted twice with DCM. The combined organic layer was dried over anhydrous Na2SC>4. After filtration and concentration, the residue was purified on a silica gel flash column with hexane: DCM (100:1-1:100) to afford the intermediate (50) as a yellow solid (5.517 g, 40% yield). 'H NMR (CDCI3, 400 MHz) d (ppm) 7.81 (d , J = 8.8 Hz, 2H), 7.61 (d , J = 8.8 Hz, 1H), 7.32-7.29 (m, 3H), 7.02-6.99 (m, 3H), 6.74 (d, J= 8.8 Hz, 2H), 3.86 (s, 3H), 3.73 (s, 3H), 2.25 (s, 3H); 13C NMR (CDCI3, 100 MHz) d (ppm) 193.15, 168.63, 159.99, 157.78, 154.38, 144.16, 140.10, 135.03, 133.76, 131.52, 130.48, 130.02, 125.76, 124.16, 121.54, 114.99, 114.13, 104.54, 55.65, 55.28, 21.16; UPLC-MS (ESP) calc, for C25H21O5S [M+l]+: 433.11, found 433.37.

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[85]Nocentini, Alessio; Ceruso, Mariangela; Bua, Silvia; Lomelino, Carrie L.; Andring, Jacob T.; McKenna, Robert; Lanzi, Cecilia; Sgambellone, Silvia; Pecori, Riccardo; Matucci, Rosanna; Filippi, Luca; Gratteri, Paola; Carta, Fabrizio; Masini, Emanuela; Selleri, Silvia; Supuran, Claudiu T. [Journal of Medicinal Chemistry, 2018, vol. 61, # 12, p. 5380 - 5394]
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[88]Current Patent Assignee: Riedel,J. D. - DE224197, 1800, C [Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 10, p. 1221][Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 10, p. 1221]
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[94]Current Patent Assignee: TRANSFUSION HEALTH LLC - WO2019/84452, 2019, A1 Location in patent: Paragraph 0432
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2
[ 2345-34-8 ]
[ 16357-40-7 ]

Yield	Reaction Conditions	Operation in experiment
80%		4-Acetoxy-benzoic acid (0.350 g, 1.95 mmol) and anhydrous AlCl3 (0.800 g, 6.02 mmol) were mixed and heated at 155-160 °C (oil bath temperature) for 5 h (after 1 h a solid, brown foamy mass formed and stirring was no longer possible). After cooling (ice bath), the reaction mixture was treated with 6.5 mL of 2 N HCl. The acidified reaction mixture was extracted with ethyl acetate (3.x.10 mL). The combined organic layer was dried over anhydrous Na2SO4, filtered, and concentrated to afford a yellow solid (0.280 g, 80percent), which was used without any further purification.

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[2]Journal of the Indian Chemical Society,1949,vol. 26,p. 235,237
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[4]Journal of the Indian Chemical Society,1984,vol. 61,p. 651
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[6]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 4954 - 4962
[7]Oriental Journal of Chemistry,2011,vol. 27,p. 1053 - 1062
[8]European Journal of Medicinal Chemistry,2015,vol. 93,p. 64 - 73

3
[ 108-24-7 ]
[ 99-96-7 ]
[ 2345-34-8 ]

Yield	Reaction Conditions	Operation in experiment
100%	With pyridine In tetrahydrofuran; toluene at 0 - 20℃; for 16h;	A.a a) p-Hydroxybenzoic acid (1.081 g, 7.8 mmol) was dissolved in a 5: 1 mixture of toluene : THF (50 mL). Pyridine (0.65 mL, 8.1 mmol) and acetic anhydride were added slowly at 0°C. The reaction mixture was stirred at room temperature for 16 hrs. Solvent was removed in vacuo. 4-Acetoxybenzoic acid was obtained in quantitative yield as a white solid and used without further purification. LC-MS: M+H+=181.0, M+Na+=203.0. 1H NMR (400 MHz, CDCIs): δ (ppm) 1 1.9 (br, 1 H, COOH), 8.13 (d, 2H, ArH), 7.17 (d, 2H, ArH), 2.31 (s, 3H).
98%	With Sulfate; titanium(IV) dioxide In cyclohexane at 81℃; for 0.166667h;
97%	With lanthanum(III) nitrate at 20℃; for 0.333333h;

97%	In acetic anhydride at 130℃; for 4h;	5.1.3. General procedure for the synthesis of compounds 4a-c General procedure: Garlic acid (2000 mg, 11.763 mmol) was dissolved in acetic anhydride(7205 mg, 70.578 mmol). The solution was then heatedunder reflux at 130 °C for 4 h, after which the deionized water(4 ml) was add to the solution to remove the unreacted acetic anhydride.The solvent was removed using a rotary evaporator underreduced pressure to yield white solid. The product was recrystallizedin CH2Cl2 and dried under vacuum. Yielding 95% compound 4a(3308 mg) as a white solid. Compounds 4b-c were synthesizedfollowing the procedure of preparation 4a.
95%	With silica gel-supported phosphotungstic acid In chloroform at 62℃; for 0.15h;
94%	With sodium hydroxide for 0.05h; Irradiation;
94%	With zirconium phosphate In neat (no solvent) at 60℃; for 2h; Green chemistry;
93%	With pyridine for 2h; Reflux;	3 4-Acetyl-benzoic acid 4-Hydroxybenzoic acid (7, 33 mmol, 4.55 g) was dissolved ina mixture of pyridine (36 mL) and acetic anhydride (3.67 g,36 mmol). The mixture was heated at reflux for 2 h, and then itwas poured into saturated aqueous NaHCO3 solution (100 mL) andthe pH was adjusted to about 2 using concentrated hydrochloricacid. The white precipitate was filtered, washed with H2O (50 mL),and dried to give pure 5 as a white solid (5.50 g, 93%), mp191e193 C. 1H NMR (500 MHz, CD3OD): d8.06 (m, J8.5, 2.5 Hz,2H), 7.21 (m, J8.5, 2.5 Hz, 2H), 2.29 (s, 3H) ppm. 13C NMR(125 MHz, CD3OD): d170.7, 169.1, 156.1, 132.4 (2C), 129.6, 123.0(2C), 21.0 ppm. HRMS (ESI): calcd for C9H9O4 [MH] 181.0501;found 181.0498.
93%	With pyridine at 50℃; for 72h;	p-Acetoxybenzoic acid (Ib) HBA (20.0 g, 0.145 mol) was suspendedin 70 mL of an Ac2O:pyridine (1:1) solution and heated to 50 Cfor 3 days. Subsequently, pouring the obtained yellowish solution into200 mL of ice-cold water resulted in the precipitation of a white solidwhich was separated by filtration after 2 h of stirring. Washing the crudeproduct several times with water yielded Ib.
93%	With pyridine at 50℃; for 72h;	p-Acetoxybenzoic acid (Ib) HBA (20.0 g, 0.145 mol) was suspendedin 70 mL of an Ac2O:pyridine (1:1) solution and heated to 50 Cfor 3 days. Subsequently, pouring the obtained yellowish solution into200 mL of ice-cold water resulted in the precipitation of a white solidwhich was separated by filtration after 2 h of stirring. Washing the crudeproduct several times with water yielded Ib. White solid. Yield 93 %. EA (calc.) for C9H8O4 (180.16): C, 60.00;H, 4.48 %; found: C, 60.09; H, 4.43 %. 1H NMR (400 MHz, DMSO-d6,298 K, ppm): δ 13.05 (s, 1H), 7.99 (d, J = 8.5 Hz, 2H), 7.26 (d, J = 8.5Hz, 2H), 2.29 (s, 3H).
92%	With Copper Zirconium Phosphate at 80℃; for 1h;	2.3. General experimental procedure for the acetylation of substrates under solvent-free conditions General procedure: ZPCu (2 mol%) was added to a mixture of phenol (1 mmol)and AA (2 mmol), and the resulting mixture was stirred at 60 °C for the specified time (Scheme 2). Upon completion of the reaction(as determined by GC), the catalyst was separated from the reaction mixture by centrifuge, then the supernatant was collected and diluted with 10% NaHCO3 solution (10 ml) before being extracted with Et2O (2 . 10 ml). The combined organic extracts were washed and then dried over anhydrous CaCl2 before being evaporated to dryness under vacuum to give the desired product. In some cases, it was necessary for the product to be purified by column chromatography over silica gel eluting with a mixture of cyclohexane and ethyl acetate.
92%	With nickel zirconium phosphate In neat (no solvent) at 60℃; for 0.5h;	General experimental procedure for the acetylation of substrates under solvent-free conditions General procedure: ZPNi (1 mol %) was added to a mixture of alcohol(1 mmol) and AA (2 mmol), and the resulting mixture was stirred at 40 °C for the specified time (Scheme 2). Upon completion of the reaction (as determined by GC), the catalyst was separated from the reaction mixture by centrifuge,then the supernatant was collected and diluted with 10 %NaHCO3 solution (10 ml) before being extracted with Et2O(2 × 10 ml). The combined organic extracts were washed and then dried over anhydrous CaCl2 before being evaporated to dryness under vacuum to give the desired product. In some cases, it was necessary for the product to be purified by column chromatography over silica gel eluting witha mixture of cyclohexane and ethyl acetate.
91%	With pyridine; aluminum(III) oxide at 95 - 99℃; for 2h; microwave irradiation;
90%	With iron zirconium phosphate In neat (no solvent) at 60℃; for 0.5h; Green chemistry;	General experimental procedure for the acetylation of substrates under solvent-free conditions General procedure: ZPFe (1 mol%) was added to a mixture of alcohol (1 mmol) and AA (2 mmol), and the resulting mixture was stirred at 40 °C for a specified time (Scheme 2). Upon completion of the reaction (as determined by gas chromatography), the catalyst was separated from the reaction mixture by centrifuge, after which the supernatant was collected and diluted with a 10% NaHCO3 solution (10 mL) before being extracted with Et2O (2 × 10 mL).The combined organic extracts were washed and then dried over anhydrous CaCl2 before being evaporated to dryness under vacuum to give the desired product. In some cases, it was necessary to purify the product by column chromatography ona silica gel column with elution by a mixture of cyclohexane and ethyl acetate.
90%	With sulfuric acid at 20℃; for 1h;
86%	With sulfuric acid at 80℃; for 3h; Inert atmosphere;	33 Preparation of 4-acetoxybenzoic acid (500-1) To a solution of 4-hydroxybenzoic acid (5 g, 36 mmol) in acetic anhydride (10 mL) was added 3 drops of cone. H2S04. The reaction mixture was heated at 80°C under N2 for 3 hr. After cooled down to room temperature, the mixture was concentrated, and then poured into ice-water. The resulting precipitate was filtered and washed with water and petroleum ether to give 4-acetoxybenzoic acid (500-1) (5.6 g, 86%) as a white solid. LC-MS (ESI): mlz (M+l) 181.2
86%	at 80℃; for 2h;	77.1 To a solution of 4-hydroxybenzoic acid (1 g, 7.24 mmol) in acetic anhydride (2 ml) were added 3 drops of concentrated sulfuric acid. The reaction mixture was heated at 80 0C for 2 h. After addition of H2O (20 ml), a solid precipitated and was filtered and washed with heptane to provide the title compound (1.12 g, 86 % yield).LC/MS: m/z 181 [M+Hf. 1H NMR (300 MHz, DMSO-d6) δ: 13.0 (1H, br s), 7.99 (2H, d, J=6.6 Hz), 7.26 (2H, d, J=6.9 Hz), 2.33 (3H, s).
85%	With anhydrous magnesium perchlorate at 20℃; for 1h;
85%	With triethylamine at 20℃; for 24h;	23 In a 50 imL round-bottomed flask fitted with condenser and magnetic stirrer were placed 4-hydroxybenzoic acid (1.50 g, 10.86 mmol), Ac2O(1.33 g, 13.03 mmol), Et^N (1.318 g, 13.03 mmol) and catalytic amount of DMAP.The reaction mixture was stirred for 24 h at rt. The reaction mixture was poured EPO into water and extracted with EtOAc. The organic layer was washed with water, dried and concentrated to give the 4-O-acetyl benzoic acid (1.66 g, 85%).
85%	In water monomer at 20 - 80℃; for 2.5h;	27 Synthesis of 4-acetoxybenzoic acid (27B) Add p-hydroxybenzoic acid (1g, 7.24mmol)Dissolve in 2mL acetic anhydride,Heat to 80°C, react for 2h,Cool to room temperature,Add 5mL water,Stir at room temperature for 30 minutes,Suction filtration, drying,1.1 g of white solid is obtained,Yield 85%
84%	at 100℃; for 4h;
83%	With toluene-4-sulfonic acid at 85℃; for 1h;	A solution of 4-hydroxybenzoic acid (3, 1.4 g, 10 mmol) in aceticanhydride (1.6 g, 16.0 mmol) and p-methylbenzenesulfonic acid(80 mg, 0.4 mmol) was allowed to stir at 85 for 1 h. After completionof the reaction, the reaction mixture was quenched by addition of waterand separated in ice-bath. The crude product was then purified by recrystallization(ethanol-water) to provide 4-acetoxybenzoic acid (1.5 g,yield 83%).
82%	With bismuth oxide perchlorate In acetonitrile at 20℃; for 1h;
82%	for 6h; Reflux;
82%	Stage #1: acetic anhydride; 4-hydroxy-benzoic acid With sulfuric acid for 1h; Stage #2: With water monomer for 3h;
82%	With sulfuric acid at 60℃; for 3h; Inert atmosphere;
80%	With pyridine In tetrahydrofuran at 20℃; for 24h;
80%	With sodium hydroxide In water monomer at 20℃; for 4h;	4-Acetoxy benzoic acid Into a 500 mL beaker, p-hydroxy benzoic acid(13.81 g, 0.1 mol) and distilled water (250 mL) wereadded and stirred to make uniform slurry. In anotherbeaker, sodium hydroxide (4.4 g, 0.11 mol) wasdissolved in distilled water (50 mL), added slowly tothe slurry and the solution stirred till completedissolution of 4-hydroxy benzoic acid to its sodiumsalt. To this solution, distilled acetic anhydride(11 mL, 0.11 mol) was added slowly and the massstirred for 4 hr at RT to obtain a precipitate of 4-acetoxy benzoic acid. The solution was filtered, theresidue washed successively with cold dilutehydrochloric acid and distilled water. The crudeproduct was purified by recrystallization frommethanol and dried under reduced pressure at 80°Cfor 8 hr. Yield: 80%; m.p. 190-92°C; IR (Nujol): 1730cm-1 [C=O stretching]; 1H NMR (DMSO-d6) : d 8.00 (d,2H), 7.30 (d, 2H), 2.30 (s, 3H) and 10.10 (s, 1H).
80%	With sodium hydroxide In water monomer at 20℃; for 4h;	2.2a 4-Acetoxy benzoic acid [4-ACBA]: In a 500 mLbeaker, 4-hydroxy benzoic acid (13.81g, 0.1 mole) and distilledwater (250 mL) were added and stirred tomake uniformslurry. In another flask, sodium hydroxide (4.4 g, 0.11 mole)was dissolved in 50 mL distilled water and was added to the slurry. The reaction mixture was stirred till 4-hydroxybenzoic acid dissolved completely, and to it distilled aceticanhydride (11.23 g, 0.11 mole) was added slowly. After theaddition of acetic anhydride, stirring was continued for 4 hat room temperature to obtain a precipitate of 4-acetoxy benzoicacid. The precipitate obtained was filtered and washedseveral times with cold dilute hydrochloric acid and distilledwater. The crude product was recrystallized from methanoland dried under reduced pressure. Yield: 80%. M.p.: 190°C, IR (Nujol, cm-1): 1730 (C=Ostretching); 1HNMR(DMSOd6,δ): 8.00(d, 2H); 7.30(2H, d); 2.30(s, 3H); 10.10(s, 1H).
78%	for 6h; Reflux;	4-Acetoxybenzoic acid A suspension of 4-hydroxybenzoic acid (1.00 g, 7.2 mmol) in acetic anhydride (2 ml) was heated under reflux for 6 h. The excess acetic anhydride was evaporated and the residue was triturated in diethyl ether, filtered off, washed with diethyl ether and dried at suction to give the product as white solid (1.10 g, 78 %), m.p., 188 °C. (lit.5 m.p. 189 °C). 1H NMR (300 MHz, CDCl3): d 8.16 (d, 2H, J = 9 Hz), 7.22 (d, 2H, J = 9 Hz), 2.34 (s, 3H).
77%	With pyridine at 20℃; for 4h;	1 Step 1 Acetic anhydride ( 10 ml) was added dropwise to a cooled solution of [98] (2.0 g, 14.49 mmol) in pyridine ( 10 ml), and stirred at RT for 4 h. The reaction mixture was cooled and poured over crushed ice. The white precipitate formed was collected by filtration, washed with diethyl ether (50 ml) and dried to afford [99] as a white solid (2.0 g, 77 %). ESIMS: 181 (M+ + 1 )
77%	With pyridine at 20℃; for 4h;
75%	for 6h; Heating;
72%	With pyridine at 20℃; for 1h;
70%	With sodium hydroxide at 20℃; for 1h;
66%	With pyridine for 2h; Inert atmosphere;	4-(Hydroxycarbamoyl)phenyl acetate (2c) A mixture of 4-hydroxybenzoic acid (1.0 g, 138.12 mmol)and acetic anhydride (5 mL) in pyridine (10 mL) wasstirred at 125 °C for 2 h, equipped with a refluxing condenserunder argon. After cooling at room temperature, themixture was quenched with saturated aqueous NaHCO3,acidified with 12 N HCl to pH 2. The resulting solid wasfiltered, washed with H2O (50 mL), and dried under highvacuum to afford compound 2c in 66% yield. 1H NMR(500 MHz, (CDCl3) δ 8.14 (d, J = 8.6 Hz, 2H), 7.21 (d,J = 8.6 Hz, 2H), 2.34 (s, 3H). 13C NMR (125 MHz,CDCl3) δ 171.0, 169.0, 155.0, 131.9, 126.9, 121.9, 21.3.ESI MS (m/e) = 179.03 [M-1]-.
66%	With pyridine at 125℃; for 2h; Inert atmosphere;	2 2. 4- (hydroxycarbamoyl) phenyl acetate [4- (Hydroxycarbamoyl) phenyl acetate; 2c] 4-hydroxybenzoic acid (1.0 g, 138.12 mmol)And acetic anhydride (5 mL)Pyridine (10 mL)The mixture was refluxed using an argon reflux condenserStirred at 125 ° C. for 2 hours,After cooling to room temperature, the reaction was stopped with saturated aqueous NaHCO 3, acidified to pH 2 by addition of 12N HCl, the solid obtained was filtered, washed with H 2 O (50 mL) and dried under high vacuum to give Compound 2c in 66% yield.
64.7%	With sulfuric acid at 80℃; for 4h;	1 General acetylation procedure General procedure: Ten grams of a monomer containing one or two hydroxyl groups were placed in a 100mL round-bottom flask on a magnetic stirring plate. Acetic anhydride was added in a slight stoichiometric excess with respect to the hydroxyl groups together with a catalytic amount of H2SO4. The mixture was heated to 80°C and stirred for 4h. After cooling to 0°C for 1h 200mL water was added to the mixture and the solution was filtered. The obtained crystals were washed with water and dried in vacuo at 40°C overnight. All acetylated monomers were recrystallized at least once before usage in polymerization.
54%	With sulfuric acid for 3h; Inert atmosphere;
	With sulfuric acid
	With benzene
	With sodium hydroxide
	With magnesium In benzene
	Ambient temperature;
	With sulfuric acid; water monomer 1) 80 deg C, 2) r.t.; Yield given. Multistep reaction;
	With sulfuric acid at 100℃; for 1h;
	With phosphoric acid at 20℃; Yield given;
	With pyridine In toluene Heating;

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[33]Ganellin, C. Robin; Fkyerat, Abdellatif; Bang-Andersen, Benny; Athmani, Salah; Tertiuk, Wasyl; Garbarg, Monique; Ligneau, Xavier; Schwartz, Jean-Charles [Journal of Medicinal Chemistry, 1996, vol. 39, # 19, p. 3806 - 3813]
[34]Elsinghorst, Paul W.; Cieslik, Julia S.; Mohr, Klaus; Tränkle, Christian; Gütschow, Michael [Journal of Medicinal Chemistry, 2007, vol. 50, # 23, p. 5685 - 5695]
[35]Uedaira, Takahiro; Koide, Naoyuki [Molecular Crystals and Liquid Crystals Science and Technology, Section A: Molecular Crystals and Liquid Crystals, 2001, vol. 365, p. 23 - 32]
[36]Lim, Jiah; Song, Yoojin; Jang, Jung-Hee; Jeong, Chul-Ho; Lee, Sooyeun; Park, Byoungduck; Seo, Young Ho [Archives of Pharmacal Research, 2018, vol. 41, # 10, p. 967 - 976]
[37]Current Patent Assignee: KEIMYUNG UNIVERSITY - KR102023845, 2019, B1 Location in patent: Paragraph 0071-0073; 0136; 0137
[38]Wilsens, Carolus H.R.M.; Noordover, Bart A.J.; Rastogi, Sanjay [Polymer, 2014, vol. 55, # 10, p. 2432 - 2439]
[39]Cho, Hanna; Cho, Kyungseon; Kim, Mi-Jin; Kim, Nam Doo; Lee, In-Kyu; Park, Sungmi; Shin, Injae; Sim, Taebo; Yoo, Eun Kyung; Yoon, Hojong [Journal of Medicinal Chemistry, 2019]
[40]Klepl [Journal fur praktische Chemie (Leipzig 1954), 1883, vol. <2> 28, p. 217]
[41]Klepl [Journal fur praktische Chemie (Leipzig 1954), 1883, vol. <2> 28, p. 217] Sava, Ion; Belomoina, Nataliya; Brumǎ, Maria [Revue Roumaine de Chimie, 2004, vol. 49, # 8, p. 695 - 703]
[42]Robertson; Robinson [Journal of the Chemical Society, 1926, p. 1715]
[43]Kauffmann [Chemische Berichte, 1909, vol. 42, p. 3481][Chemisches Zentralblatt, 1906, vol. 77, # I, p. 551]
[44]Lesser; Gad [Chemische Berichte, 1926, vol. 59, p. 234]
[45]Kraus; Femfert [Hoppe-Seyler's Zeitschrift fur Physiologische Chemie, 1976, vol. 357, # 7, p. 937 - 947]
[46]Vera, S.; Rodenas, E. [Tetrahedron, 1986, vol. 42, # 1, p. 143 - 150] Vera, S.; Rodenas, E. [Journal of Physical Chemistry, 1986, vol. 90, # 15, p. 3414 - 3417]
[47]Gazit, Aviv; Yaish, Pnina; Gilon, Chaim; Levitzki, Alexander [Journal of Medicinal Chemistry, 1989, vol. 32, # 10, p. 2344 - 2352]
[48]Desai, J. M.; Marjadi, S. I.; Desai, C. M. [Journal of the Indian Chemical Society, 1993, vol. 70, # 1, p. 65 - 66]
[49]Robinson; Smith [Journal of Pharmacy and Pharmacology, 1984, vol. 36, # 3, p. 157 - 162]
[50]Cheng, Si-Xue; Chung, Tai-Shung [Journal of Physical Chemistry B, 1999, vol. 103, # 23, p. 4923 - 4932]

4
[ 140-39-6 ]
[ 2345-34-8 ]

Yield	Reaction Conditions	Operation in experiment
90%	With (trifluoromethyl)benzene; bromine In lithium hydroxide monohydrate at 20℃; for 24h; Irradiation;	General procedure of oxidation of toluenes into carboxylic acids General procedure: A 100-mL-pyrex flask was charged with 1 (5.0 mmol) and Br2 (840 mg, 10.5 mmol) in BTF (30 mL) andwater (6 mL). The attached reflux condenser was open air, and the flask was irradiated with a 13-Wwhite-fluorescent lamp, 40-W-blue LED (454 nm), or 10-W-UV LED (385 nm) at intervals of 5 cm withvigorous stirring for 24 h. Saturated aqueous NaHCO3 and EtOAc were added to the reaction mixture.The alkaline aqueous layer was separated and acidified with diluted HCl. The solution was successivelyextracted using EtOAc and washed with water and brine. A concentrated product 2 was produced afterdrying over anhydrous Na2SO4. The samples were sufficiently pure, without requiring furtherpurification.
83%	With zinc oxide In N,N-dimethyl-formamide for 0.133333h; microwave irradiation;
83%	With oxygen; manganese (II) acetate tetrahydrate; Co(OAc)₂.4H₂O; glacial acetic acid at 100℃; for 15h;

80%	With cerium(III) trichloride; 1,1,1-trichloroethanol; oxygen In acetonitrile at 60℃; Irradiation;
74%	With azobisisobutyronitrile; oxygen; N,N′,N″-trihydroxyisocyanuric acid In glacial acetic acid at 100℃; for 6h;
50%	With tert.-butylhydroperoxide; Ru^III-Montmorillonite K₁₀ In acetonitrile for 4h; Heating;
47%	With potassium permanganate; benzyltriethylammonium permanganate In glacial acetic acid at 30℃; for 72h;
	With oxygen; cobalt(II) diacetate; ozone; glacial acetic acid at 95℃; for 1h;

Reference： [1]Kirihara, Masayuki; Sakamoto, Yugo; Yamahara, Sho; Kitajima, Atsuhito Kitajima; Kugisaki, Naoki; Kimura, Yoshikazu [Synlett, 2022]
[2]Gupta, Monika; Paul, Satya; Gupta, Rajive; Loupy, André [Tetrahedron Letters, 2005, vol. 46, # 30, p. 4957 - 4960]
[3]Location in patent: experimental part Nakamura, Ryota; Obora, Yasushi; Ishii, Yasutaka [Tetrahedron, 2009, vol. 65, # 18, p. 3577 - 3581]
[4]Wang, Chang-Cheng; Zhang, Guo-Xiang; Zuo, Zhi-Wei; Zeng, Rong; Zhai, Dan-Dan; Liu, Feng; Shi, Zhang-Jie [Science China Chemistry, 2021, vol. 64, # 9, p. 1487 - 1492]
[5]Hirai, Naruhisa; Sawatari, Naoko; Nakamura, Norihiro; Sakaguchi, Satoshi; Ishii, Yasutaka [Journal of Organic Chemistry, 2003, vol. 68, # 17, p. 6587 - 6590]
[6]Nikalje, Milind D.; Sudalai [Tetrahedron, 1999, vol. 55, # 18, p. 5903 - 5908]
[7]Sangaiah, R.; Rao, G.S.Krishna [Synthesis, 1980, # 12, p. 1018 - 1019]
[8]Location in patent: experimental part Galstyan; Tarasenko; Shumilova [Russian Journal of Applied Chemistry, 2008, vol. 81, # 10, p. 1865 - 1867]

5
[ 108-24-7 ]
[ 123-08-0 ]
[ 2345-34-8 ]

Yield	Reaction Conditions	Operation in experiment
93%	With oxygen In 1,2-dichloro-ethane at 25℃;
93%	With oxygen In 1,2-dichloro-ethane at 25℃; for 20h;

Reference： [1]Bhatia, Beena; Iqbal, Javed [Tetrahedron Letters, 1992, vol. 33, # 51, p. 7961 - 7964]
[2]Bhatia, Beena; Punniyamurthy, T.; Iqbal, Javed [Journal of Organic Chemistry, 1993, vol. 58, # 20, p. 5518 - 5523]

6
[ 75-36-5 ]
[ 99-96-7 ]
[ 2345-34-8 ]

Yield	Reaction Conditions	Operation in experiment
98.6%	With pyridine In tetrahydrofuran for 1h; Cooling with ice;	3 In a dry 50 ml round bottom flask was added 5 g (0.036 mol) of p-hydroxybenzoic acid (PHB)25 mL of anhydrous tetrahydrofuran, Stirring the solution into a uniform and transparent,After the addition of 4.04 ml (0.06 mol) of pyridine,After the reaction was completed, the reaction mixture was washed twice with deionized water and suction-filtered to give the desired product, acetoxybenzoic acid, which was naturally air-dried and then dried in vacuo. The oven was dried for 24 h to give 6. 346 g of the desired product in 98.6% yield.
97%	In cyclohexane at 30 - 40℃; for 2h;	1.1 Example 1 To 100 ml of cyclohexane was added 51.8 g (0.375 mol) of p-hydroxybenzoic acid,35.30 g (0.45 mol) of acetyl chloride was added dropwise at 30 to 35 ° C,Dropwise at 35 ~ 40° C reaction was incubated 2h. Atmospheric distillation to recover excess acetyl chloride and solvent cyclohexane,Recrystallization from ethanol gave 65.5 g of p-acetoxybenzoic acid in 97% yield;
82.3%	In pyridine at 0 - 20℃; for 1.58333h;	41 To a mixture of 4-hydroxybenzoic acid (16) (20.0 g, 144.8 mmol) and pyridine (60 ml, 742 mmol) at 0°C was added acetyl chloride (12 ml, 169 mol) over 5 minutes. The resulting mixture was stirred at ice bath temperature for 30 minutes and for 1 hour at room temperature. The mixture was poured into ice water (500 ml) and the pH of the medium was brought to 1-2 by adding conc. HCl (ca. 40 ml). The precipitate was filtered, washed with water (100 ml), and dried (Na2S04). The obtained solid material was crystallized from methanol-water (1 : 1) (200 ml) affording the title compound (21.485 g, 82. 3%) as white crystals, m. p. 181-183°C. 1H NMR (CDCl3, HMDSO) δ: 2.32 (3H, s); 7.22 (2H, d, J=8. 2 Hz) ; 8.16 (2H, d, J=8. 2 Hz) ; 10.50 (1 H, br s).

	In benzene Heating;
	With triethylamine
	With pyridine at 0 - 20℃;

Reference： [1]Current Patent Assignee: CHINA PETROCHEMICAL CORPORATION - CN103626659, 2016, B Location in patent: Paragraph 0026; 0027
[2]Current Patent Assignee: RUDONG JINKANGTAI CHEMICAL - CN107129432, 2017, A Location in patent: Paragraph 0018; 0019; 0024; 0029; 0034; 0039
[3]Current Patent Assignee: ONXEO - WO2004/65354, 2004, A1 Location in patent: Page 125; 126; 78; 85
[4]Jiang, Xi-Kui; Hui, Yong-Zheng; Fan, Wei-Qiang [Journal of the American Chemical Society, 1984, vol. 106, # 13, p. 3839 - 3843]
[5]Current Patent Assignee: LG CHEM CO.,LTD. - US2016/145187, 2016, A1 Location in patent: Paragraph 0085; 0092
[6]Guo, Xuliang; Xing, Qingyu; Lei, Kunhua; Zhang-Negrerie, Daisy; Du, Yunfei; Zhao, Kang [Advanced Synthesis and Catalysis, 2017, vol. 359, # 24, p. 4393 - 4398]

7
[ 21867-64-1 ]
[ 2345-34-8 ]
[ 736910-19-3 ]

Reference： [1]European Journal of Medicinal Chemistry,1996,vol. 31,p. 895 - 899

8
[ 2628-16-2 ]
[ 2345-34-8 ]

Yield	Reaction Conditions	Operation in experiment
88%	With Oxone; 2-iodo-3,4,5,6-tetramethylbenzoic acid In water; acetonitrile for 19h;
80%	With tert.-butylhydroperoxide In water at 50℃; for 12h; Sealed tube; Green chemistry;
75%	With Oxone In N,N-dimethyl-formamide at 25℃; for 3h;

30%	With ammonium thiocyanate; oxygen In acetic acid at 25℃; for 8h;	General procedure for the preparation of compound 3 General procedure: Themixture of styrene (2.0 mmol) and ammonium thiocyanate (1.0 mmol) in HOAc (3mL) was stirred in oxygen atmosphere at 25 oC for 8 h. After removalof solvent under reduced pressure, the residue waspurified by flash silica-gel column chromatography (eluted with petroleum ether/ acetone from 50/1 to 8/1 (v:v)) and afforded the desired phenacylthiocyanate 3. 4.3.5 4′-Acetoxybenzoic acid (3h)11 (0013) Yellow oil (54mg, 30% yield). 1H NMR (400MHz, CDCl3): δ 9.99 (s, 1H), 7.92 (d, J=8.0Hz, 2H), 7.28 (d, J=8.0Hz, 2H), 2.34 (s, 3H). 13C NMR (150MHz, CDCl3): δ 190.9, 168.7, 155.3, 134.0, 131.2, 122.4, 21.2. MS (ESI-TOF) m/z: (M+H)+ calcd for C9H9O4 181.0, found 181.0
	With 1,2-dibutoxyethane; oxygen at 110℃; for 12h;

Reference： [1]Moorthy, Jarugu Narasimha; Parida, Keshaba Nanda [Journal of Organic Chemistry, 2015, vol. 79, # 23, p. 11431 - 11439]
[2]Upadhyay, Rahul; Rana, Rohit; Sood, Aakriti; Singh, Vikash; Kumar, Rahul; Srivastava, Vimal Chandra; Maurya, Sushil K. [Chemical Communications, 2021, vol. 57, # 44, p. 5430 - 5433]
[3]Kwangyeol, Lee; Kim, Yong-Ho; Han, Soo Bong; Kang, Hongkyu; Park, Soyoung; Seo, Won Seok; Park, Joon T.; Kim, Bongsoo; Chang, Sukbok [Journal of the American Chemical Society, 2003, vol. 125, # 23, p. 6844 - 6845]
[4]Liu, Kui; Li, Da-Peng; Zhou, Shao-Fang; Pan, Xiang-Qiang; Shoberu, Adedamola; Zou, Jian-Ping [Tetrahedron, 2015, vol. 71, # 23, p. 4031 - 4034]
[5]Ou, Jinhua; Tan, Hong; He, Saiyu; Wang, Wei; Hu, Bonian; Yu, Gang; Liu, Kaijian [Journal of Organic Chemistry, 2021, vol. 86, # 21, p. 14974 - 14982]

9
[ 2345-34-8 ]
[ 35354-29-1 ]
polymer; monomer(s): 4-acetoxybenzoic acid; 3,5-diacetoxybenzoic acid, feed molar part 0.05 [ No CAS ]

Reference： [1]Macromolecules,2004,vol. 37,p. 1463 - 1469

10
[ 2345-34-8 ]
[ 35354-29-1 ]
polymer; monomer(s): 4-acetoxybenzoic acid; 3,5-diacetoxybenzoic acid, feed molar part 0.10 [ No CAS ]

Reference： [1]Macromolecules,2004,vol. 37,p. 1463 - 1469

11
[ 2345-34-8 ]
[ 35354-29-1 ]
polymer; monomer(s): 4-acetoxybenzoic acid; 3,5-diacetoxybenzoic acid, feed molar part 0.15 [ No CAS ]

Reference： [1]Macromolecules,2004,vol. 37,p. 1463 - 1469

12
[ 2345-34-8 ]
[ 35354-29-1 ]
polymer; monomer(s): 4-acetoxybenzoic acid; 3,5-diacetoxybenzoic acid, feed molar part 0.20 [ No CAS ]

Reference： [1]Macromolecules,2004,vol. 37,p. 1463 - 1469

13
[ 2345-34-8 ]
[ 123-08-0 ]
[ 219502-21-3 ]

Yield	Reaction Conditions	Operation in experiment
53%	With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 24h;
50.7%	With dmap; dicyclohexyl-carbodiimide In dichloromethane at 25℃;	I-2.1 Step 1. Synthesis of 4-formylphenyl 4-acetoxybenzoate I-2b The mixture of 4-acetoxybenzoic acid (5.00 g, 27.753 mmol, 1.00 eq), P- hydroxybenzaldehyde (4.07 g, 33.30 mmol, 1.20 eq), dicyclohexylcarbodiimide (8.59 g,41.63 mmol, 1.50 eq) and DMAP (0.34 g, 2.775 mmol, 0.10 eq) in DCM (20.00 mL) was stirred overnight at 25° C. The mixture was then quenched by the addition of 1000 mL of ice water and extracted with 3x1 L of ethyl acetate, the organic layers were combined and dried over anhydrous sodium sulfate. Filtered, the filtrate was concentrated to give a residue, after purification by chromatography eluting with ethyl acetate/petroleum ether (1/5), 4 g (50.70%) of 4-formylphenyl 4-(acetyloxy)benzoate was obtained. 1H NMR (400 MHz, DMSO-d6) δ 10.05 (s, 1H), 8.24 - 8.19 (m, 2H), 8.05 (d, J = 8.6 Hz, 2H), 7.57 (d, J = 8.2 Hz, 2H), 7.41 (d, J = 8.2 Hz, 2H), 2.34 (s, 3H).

Reference： [1]Chang-Xiao; Mouscadet, Jean-Francois; Chiang, Chih-Chia; Tsai, Hou-Jen; Hsu, Ling-Yih [Chemical and Pharmaceutical Bulletin, 2006, vol. 54, # 5, p. 682 - 686]
[2]Current Patent Assignee: BEIJING XUANYI PHARMASCIENCES - WO2021/178818, 2021, A2 Location in patent: Paragraph 00524; 00525

14
[ 2345-34-8 ]
[ 131631-89-5 ]

Reference： [1]Journal of Medicinal Chemistry,1993,vol. 36,p. 2011 - 2017

15
[ 2345-34-8 ]
[ 32136-81-5 ]

Reference： [1]Journal of the Chemical Society,1926,p. 1715

16
[ 335255-43-1 ]
[ 2345-34-8 ]
[ 849236-42-6 ]

Yield	Reaction Conditions	Operation in experiment
36%	With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; In pyridine; at 20℃;	Step 1: Acetic acid 4-(2-TERT-BUTOXYCARBONYLAMINO-5-THIOPHEN-2-YL-PHENYLCARBAMOYL)-PHENYL ester (183) [0346] TERTBUTYL 2-AMINO-4-(THIOPHEN-2-YL) PHENYLCARBAMATE 178 (0.198g, 0.68 MMOL), BENZOTRIAZOL-1-YLOXY-TRIS (DIMETHYLAMINO) PHOSPHONIUM HEXAFLUOROPHOSPHATE (BOP) (0.302g, 0.68 MMOL) and 4-acetoxybenzoic acid (182) (0. 123G, 0.68 MMOL) were stirred in pyridine at rt overnight then solvent evaporated and purified by flash chromatography (35% ethyl acetate in hexanes) to provide 183 (O. 11g, 36%). 1H NMR: (DMSO) 5 (ppm): 400 MHz, (DMSO) d (ppm): 9.91 (s, 1H), 8.72 (s, 1H), 8.01 (d, J= 8.8 Hz, 2H), 7.78 (d, J= 1.8 Hz, 1H), 7.63 (d, J= 8. 4 Hz, 1H), 7.51 (dd, J= 4.9, 0.98 Hz, 2H), 7.44 (dd, J= 3.7, 0.98 Hz, 1H), 7.30 (d, J= 8.6 Hz, 1H), 7.11 (dd, J= 5.1 Hz, 1H), 2.32 (s, 3H), 1.46 (s, 9H). MS: (CALC.) 452.14 ; (obt. ) 475 (M+Na).

Reference： [1]Patent: WO2005/30704,2005,A1 .Location in patent: Page/Page column 203; 205

17
[ 27914-73-4 ]
[ 2345-34-8 ]
[ 18733-06-7 ]
[ 140234-32-8 ]

Yield	Reaction Conditions	Operation in experiment
70.8%	With pyridine; thionyl chloride In 1,4-dioxane; (2S)-N-methyl-1-phenylpropan-2-amine hydrate; N,N-dimethyl-formamide; benzene	1 EXAMPLE 1 STR78 In a 20 ml round-bottom flask, 2.90 g (16.1 m mole) of 4-acetoxybenzoic acid and 3.7 ml of thionyl chloride were placed. To the mixture two drops of N,N-dimethylformamide was added at room temperature under stirring followed by refluxing and stirring for 20 minutes. After the reaction, dry benzene was added into the reaction mixture. Excessive thionyl chloride was distilled off under reduced pressure, followed by distilling-off thereof with benzene. This operation was repeated twice. In a 100 ml round-bottom flask, the resultant 4-acetoxybenzoic chloride, 3.10 g (15.1 m mole) of 2-amino-4-octylphenol and 40 ml of dioxane were placed and heated to keep inner temperature 85 to 88.5° C. To the mixture, 5.5 ml of pyridine was added dropwise under stirring, followed by heating and stirring for 20 minutes at 85 to 88.5° C. After the reaction, the reaction mixture was cooled with ice and poured into ca. 200 ml of ice water to precipitate a crystal. The crystal was filtered, washed and recrystallized from methanol to obtain 4.10 g of 2-(4-acetoxybenzoylamino)-4-octylphenol (Yield: 70.8%).

Reference： [1]Current Patent Assignee: CANON INC. - US5244596, 1993, A

18
[ 2345-34-8 ]
[ 118-93-4 ]
C₁₇H₁₄O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With pyridine; trichlorophosphate at 20℃; for 24h;	23 To a 100 mL round-bottomed flask fitted with condenser and magnetic stirrer were placed 2'-hydroxyacetophenone (1.25 g, 9.16 mmol), 4-O- acetylbenzoic acid (4.0 g, 9.16 mmol) and pyridine (25 mL). POCI3 (1.4 g, 9.16mmol) was added slowly on cooling. The reaction mixture was stirred for 24 h at rt under nitrogen. The reaction mixture was poured into ice water and extracted with EtOAc. The organic layer was washed with water, dried and concentrated to give product (1.7 g, 85%). To the product (1.7 g, 5.69 mmol) in THF (30 mL) was added a potassium t-butoxide (0.836 g, 6.83 mmol) and the reaction mixture was stirred for 24 h at rt under N2. The reaction mixture was poured into saturatedaqueous solution of NH4CI. The organic layer was separated, washed with water,dried and concentrated to give the crude product. Purification by column chromatography using 20% EtOAc in hexane to give 200 mg of product (14%). MS (ES) m/z: 257.08 (M+1 ).

Reference： [1]Current Patent Assignee: RESVERLOGIX CORP - WO2006/45010, 2006, A2 Location in patent: Page/Page column 177

19
[ 13031-43-1 ]
[ 2345-34-8 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen bromide; acetic anhydride; acetic acid; In titanium-clad;	EXAMPLE IV One hundred and sixty-six (166) g (0.933 mole) of p-acetoxyacetophenone, 100 g (0.98 mole) of acetic anhydride, 250 g (4.17 moles) of acetic acid, 1.2 g (0.0048 mole) of Co(OAc)2.4H2 O, 1.2 g (0.0049 mole) of Mn(OAc)2.4H2 O, and 1.6 g (0.01 mole) of 48% HBr were combined in a two-liter titanium-clad autoclave. The mixture was heated to 300 F. and pressurized to 300 psi. Air was introduced at a rate of 0.75 scf/min for the first fifteen minutes and then lowered to 0.63 scf/min for the remainder of the reaction. During the oxidation, a mixture of 140 g (1.37 moles) of acetic anhydride and 35 g (0.58 mole) of acetic acid was added through a pump. The oxidation ran for 31 minutes. The reaction solution was cooled and evaporated from 678 g to 579 g. The precipitated p-acetoxybenzoic acid was filtered and dried to yield 106 g with a purity of 96.4 mole % (61 mole % yield). Analysis of the filtrate showed: p-acetoxybenzoic acid, 18.2 mole %, p-acetoxyacetophenone, 2.4 mole %, p-hydroxybenzoic acid, 1.3 mole %. Analysis of the reactor wash showed p-acetoxybenzoic acid, 2.2 mole %. Total reaction yield of p-acetoxybenzoic acid was 81.4 mole %.
	With hydrogen bromide; acetic anhydride; acetic acid; In titanium-clad;	EXAMPLE V One hundred and sixty-six (166) g (0.933 mole) of p-acetoxyacetophenone, 100 g (0.98 mole) of acetic anhydride, 250 g (4.17 moles) of acetic acid, 0.35 g (0.0014 mole) of Co(OAc)2.4H2 O, 0.35 g (0.0014 mole) of Mn(OAc)2.4H2 O, and 0.47 g (0.0028 mole) of 48% HBr were combined in a two-liter titanium-clad autoclave. The mixture was heated to 300 F. and pressurized to 300 psi. Air was introduced at a rate of 0.75 scf/min for 15 minutes and then lowered to 0.61 scf/min for the remainder of the reaction. During the run, a solution of 150 g (1.47 moles) of acetic anhydride and 38 g (0.63 mole) of acetic acid was added through a pump. The run time was 31 minutes. The reaction solution was concentrated by evaporating acetic acid from 696 g to 660 g. The precipitated p-acetoxybenzoic acid was isolated by filtration and dried to give 81.3 g of 97.6 mole % purity (47.2 mole % yield). Analysis of the filtrate showed: p-acetoxybenzoic acid, 32 mole %, p-hydroxybenzoic acid, 0.3 mole %, and p-acetoxyacetophenone, 3.2 mole %. Analysis of the reactor wash showed p-acetoxyacetophenone, 2.1 mole %. Total reaction yield of p-acetoxybenzoic acid was 81.3 mole %.

Reference： [1]Advanced Synthesis and Catalysis,2009,vol. 351,p. 1677 - 1684
[2]Patent: US4873361,1989,A
[3]Patent: US4873361,1989,A
[4]Organic Process Research and Development,2004,vol. 8,p. 163 - 168

20
[ 13031-43-1 ]
[ 2345-34-8 ]
[ 99-96-7 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen bromide; acetic anhydride; acetic acid; In titanium-clad;	EXAMPLE VI One hundred and sixty-six (166) g (0.933 mole) of p-acetoxyacetophenone, 100 g (0.98 mole) of acetic anhydride, 250 g (4.17 moles) of acetic acid, 3.5 g (0.0014 mole) of Co(OAc)2.4H2 O, 3.5 g (0.0014 mole) of Mn(OAc)2.4H2 O, and 4.7 g (0.0028 mole) of 48% HBr were combined in a two-liter titanium-clad autoclave. The reaction mixture was heated to 300 F. and pressurized to 300 psi. Air was introduced at a rate of 0.75 scf/min. During the run, a solution of 54 g (0.53 mole) of acetic anhydride and 13 g (0.217 mole) of acetic acid was added through a pump. The run time was 25 minutes. Analyses of the total reactor effluent and wash showed: p-acetoxybenzoic acid, 87 mole % yield, p-hydroxybenzoic acid, 1.2 mole % yield, and p-acetoxyacetophenone, 3.5 mole % yield.

Reference： [1]Patent: US4873361,1989,A

21
[ 2345-34-8 ]
[ 13031-43-1 ]
[ 99-96-7 ]

Yield	Reaction Conditions	Operation in experiment
	With acetic anhydride; acetic acid;	EXAMPLE II The oxidation of p-acetoxyacetophenone proceeded as in Example I, except that the reaction was run for 30 minutes and a total of 150 g (1.47 moles) of acetic anhydride and 37 g (0.62 mole) of acetic acid was added through the pump. The reaction mixture was concentrated from 772 g to 413 g by evaporation of acetic acid. The slurry was filtered to remove precipitated p-acetoxybenzoic acid. After drying, 128.2 g of p-acetoxybenzoic acid of 95 mole % purity (73% yield) were obtained. Remaining in the filtrate were: p-acetoxybenzoic acid, 8.5 mole % yield, p-acetoxyacetophenone, 1.8 mole % yield, p-hydroxybenzoic acid, 0.6 mole % yield.

Reference： [1]Patent: US4873361,1989,A

22
[ 13031-43-1 ]
[ 99-93-4 ]
[ 2345-34-8 ]
[ 99-96-7 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen bromide; acetic anhydride; acetic acid;	EXAMPLE VII Seventeen and one-tenth (17.1) g (0.096 mole) of p-acetoxyacetophenone, 17.1 g (0.17 mole) of acetic anhydride, 65 g (1.08 moles) of acetic acid, 0.51 g (0.002 mole) of Co(OAc)2.4H2 O, 0.50 g (0.002 mole) of Mn(OAc)2.4H2 O, and 0.68 g (0.004 mole) of 48% HBr were combined in a glass reactor and heated to 100 C. Air was introduced at a rate of 50 ml/min. After 164 hours of reaction time, the oxidation ceased. Analysis of the reaction solution showed 3.4 wt % p-acetoxyacetophenone and 2.7 wt % p-hydroxyacetophenone. In addition, p-acetoxybenzoic acid and p-hydroxybenzoic acid were present in substantial amounts. An additional 30 g (0.294 mole) of acetic anhydride were added and the oxidation reaction continued. Final reaction time was 240 hours. Analysis of the final reaction mixture showed 41 mole % yield of p-acetoxybenzoic acid, 3.9 mole % yield of p-hydroxybenzoic acid, and 1.0 mole % yield unreacted p-acetoxyacetophenone.

Reference： [1]Patent: US4873361,1989,A

23
[ 2345-34-8 ]
[ 75-36-5 ]
[ 16357-40-7 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride;AlCl3; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; 1,2,4-Trichlorobenzene;	a 3-Acetyl-4-hydroxybenzoic Acid 36.6 g (0.274 mol) of AlCl3 are suspended in 50 ml of 1,2,4-trichloro-benzene and treated with 9 g (50 mmol) of 4-acetoxybenzoic acid. After dropwise addition of 7.84 g (0.1 mol) of acetyl chloride, the reaction mixture is heated to 130-140° C., the evolution of HCl gas occurring from approximately 60° C. The mixture is stirred for approximately 1 hour at 130° C. and then allowed to cool to 60-70° C., and the mixture is poured cautiously into stirred ice water. It is extracted several times with ethyl acetate, then the combined organic phases are extracted with saturated aqueous sodium bicarbonate solution and the combined aqueous phases are adjusted carefully to pH<1 using concentrated HCl, the 3-acetyl-4-hydroxybenzoic acid separating as sparingly soluble material. Colorless crystalline substance, melting point 228-233° C.

Reference： [1]Patent: US6191164,2001,B1

24
[ 2345-34-8 ]
[ 693-02-7 ]
[ 1137972-61-2 ]
[ 1137972-63-4 ]
[ 1137972-59-8 ]

Yield	Reaction Conditions	Operation in experiment
	With [RuCl₂(p-cymene)(P(Fur)3)]; sodium carbonate In toluene at 160℃; for 0.333333h; Inert atmosphere; Microwave irradiation; regioselective reaction;
	With [RuCl₂(p-cymene)(PPh₃)] In toluene at 160℃; for 0.333333h; Inert atmosphere; regioselective reaction;
	With [RuCl₂(p-cymene)(P(Fur)3)]; sodium carbonate In toluene at 60℃; for 24h; Inert atmosphere; regioselective reaction;

1: 97.5 %Chromat. 2: 2 %Chromat. 3: 0.5 %Chromat.	With C₁₈H₃₁Cl₂PRu; water; sodium carbonate In toluene at 60℃; for 25h; Inert atmosphere;
	With [RuCl(4-isopropyltoluene)(1,3-di(2,4,6-trimethylphenyl)-imidazolinium-2-dithiocarboxylate)]PF₆; sodium carbonate In water; toluene at 60℃; for 200h; Inert atmosphere; optical yield given as %de;
	With [RuCl(4-isopropyltoluene)(1,3-di(2,6-dicyclohexyl)-imidazolium-2-dithiocarboxylate)]PF₆; sodium carbonate In water; toluene at 160℃; for 0.5h; Inert atmosphere; In sealed tube; optical yield given as %de;
	With [RuCl₂(N,N′-bis(cyclohexyl)-imidazol-2-ylidene)(p-cymene)] In water; toluene at 160℃; for 0.0833333h; Inert atmosphere; Microwave irradiation; optical yield given as %de;
	With [RuCl₂(p-cymene)-(SOC*ICy)]; sodium carbonate In water; toluene at 140℃; for 0.166667h; Inert atmosphere;
	With [RuCl₂(p-cymene)-(SOC*SIMes)]; sodium carbonate In water; toluene at 60℃; for 50h; Inert atmosphere;
	With [RuCl₂(p-cymene)(SOC*SIDip)]; sodium carbonate In water; toluene at 140℃; for 0.166667h; Inert atmosphere;
	With dichlororuthenium(II) (p-cymene)(1,3,5-triaza-7-phosphaadamantane); sodium carbonate In toluene at 160℃; for 0.5h; Inert atmosphere; Microwave irradiation; Overall yield = 97 %Chromat.;	Microwave-assisted reactions General procedure: A 10-mL glass vial containing a Teflon-coated stir bar wascharged with the carboxylic acid (0.5 mmol, 1 equiv.),the catalyst (0.004 mmol, 1/125 equiv.) and Na2CO3(0.008 mmol, 2/125 equiv.). The tube was then purged ofair by three vacuum-nitrogen cycles. A stock solution(2.6 mL) containing 1-hexyne (0.75 mmol, 1.5 equiv.)and isooctane (internal standard) in toluene was addedunder nitrogen atmosphere. The tube was then sealed andheated to 160 °C (monitored by IR sensor) under a nitrogenatmosphere in a CEM Discover instrument with 150 Wmicrowave power. After a given reaction time, the tube wascooled under a flow of compressed air, and the reactionmixture was analyzed by gas chromatography (GC).This methodology was applied for the addition of benzoicacid to propargylic alcohol and cyclization of 4-pentynoicacid. Spectral information of isolated products issimilar to those reported in the literature, [40] and [41],respectively.

Reference： [1]Location in patent: experimental part Nicks, Franois; Libert, Lionel; Delaude, Lionel; Demonceau, Albert [Australian Journal of Chemistry, 2009, vol. 62, # 3, p. 227 - 231]
[2]Location in patent: experimental part Nicks, Franois; Libert, Lionel; Delaude, Lionel; Demonceau, Albert [Australian Journal of Chemistry, 2009, vol. 62, # 3, p. 227 - 231]
[3]Location in patent: experimental part Nicks, Franois; Libert, Lionel; Delaude, Lionel; Demonceau, Albert [Australian Journal of Chemistry, 2009, vol. 62, # 3, p. 227 - 231]
[4]Nicks, Francois; Aznar, Rosario; Sainz, Daniel; Muller, Guillermo; Demonceau, Albert [European Journal of Organic Chemistry, 2009, # 29, p. 5020 - 5027]
[5]Location in patent: experimental part Willem, Quentin; Nicks, François; Sauvage, Xavier; Delaude, Lionel; Demonceau, Albert [Journal of Organometallic Chemistry, 2009, vol. 694, # 25, p. 4049 - 4055]
[6]Location in patent: experimental part Willem, Quentin; Nicks, François; Sauvage, Xavier; Delaude, Lionel; Demonceau, Albert [Journal of Organometallic Chemistry, 2009, vol. 694, # 25, p. 4049 - 4055]
[7]Location in patent: experimental part Willem, Quentin; Nicks, François; Sauvage, Xavier; Delaude, Lionel; Demonceau, Albert [Journal of Organometallic Chemistry, 2009, vol. 694, # 25, p. 4049 - 4055]
[8]Location in patent: scheme or table Hans, Morgan; Willem, Quentin; Wouters, Johan; Demonceau, Albert; Delaude, Lionel [Organometallics, 2011, vol. 30, # 22, p. 6133 - 6142]
[9]Location in patent: scheme or table Hans, Morgan; Willem, Quentin; Wouters, Johan; Demonceau, Albert; Delaude, Lionel [Organometallics, 2011, vol. 30, # 22, p. 6133 - 6142]
[10]Location in patent: scheme or table Hans, Morgan; Willem, Quentin; Wouters, Johan; Demonceau, Albert; Delaude, Lionel [Organometallics, 2011, vol. 30, # 22, p. 6133 - 6142]
[11]Musengimana, Eric; Fatakanwa, Claver [Journal of the Iranian Chemical Society, 2016, vol. 13, # 2, p. 253 - 259]

25
[ 2345-34-8 ]
[ 6309-46-2 ]

Yield	Reaction Conditions	Operation in experiment
46%	Stage #1: 4-acetyloxy-benzoic acid With borane-THF In tetrahydrofuran at 10 - 22℃; Stage #2: With water In tetrahydrofuran	-(Hvdroxymethyl)phenylacetate4- Acetoxy benzoic acid (1 g, 5.55 mmol) was dried at 0.01 mbar for 30 min and afterwards dissolved in THF (7.5 ml) and cooled down to 10°C. BH3*THF complex (1 M, 12.07 ml, 12.07 mmol) in THF was added dropwise over 10 min time period. The reaction mixture was stirred over night at 22 °C. Further, water (4.34 ml) was slowly added to stop the reaction and the all volatiles were removed. Colorless product obtained was extracted using water, ethyl acetate mixture. The organic phase was washed with water (3 x 30 ml), saturated NaCI solution (3 x 70ml) and dried over Na2S04. After removing the solvent, the product was purified by using column chromatography on silica gel and CH2CI2 / ethyl acetate / triethylamine (10:4:0.5, v/v/v) mixture as an eluent. The product is crystalline, colorless solid. Yield was 0.42 g, 2.53 mmol (46 %): TLC-analysis on silica plates: Rf = 0.41 in (CH2CI2 / ethyl acetate / triethylamine (10:4:0.5, v/v/v)).
41%	With borane-THF In tetrahydrofuran at 22℃; for 36h;

Reference： [1]Current Patent Assignee: HEIDELBERG UNIVERSITY - WO2012/123076, 2012, A1 Location in patent: Page/Page column 27-28
[2]Marzenell, Paul; Hagen, Helen; Sellner, Leopold; Zenz, Thorsten; Grinyte, Ruta; Pavlov, Valeri; Daum, Steffen; Mokhir, Andriy [Journal of Medicinal Chemistry, 2013, vol. 56, # 17, p. 6935 - 6944]

26
[ 2345-34-8 ]
[ 551-93-9 ]
[ 69181-52-8 ]

Yield	Reaction Conditions	Operation in experiment
81%	Stage #1: 4-acetyloxy-benzoic acid With thionyl chloride; N,N-dimethyl-formamide at 20℃; Reflux; Stage #2: 2-aminoacetophenone With triethylamine In dichloromethane at 20℃; Cooling with ice; Stage #3: With sodium hydroxide In methanol; water at 20℃;	General procedure for 4-hydroxyl benzoyl aromatic amine (11) General procedure for 4-hydroxyl benzoyl aromatic amine (11) To a suspension of 4-acetoxybenzoic acid (50 mmol) and SOCl2 (20 ml), DMF (0.5 ml) was added dropwise as catalyst. After stirring for a few minutes at room temperature, the solution became clear and was then heated at reflux for 2 h. After evaporating under reduced pressure, the solution was added dropwise to the mixture of o-aminoacetophenone (45 mmol), NEt3 (100 mmol) and anhydrous CH2Cl2 (60 mL) in an ice bath. The reaction was continuously stirred at room temperature overnight. The solid was obtained by evaporation under reduced pressure and dissolved in MeOH/H2O (V/V = 1/1, 100 ml). Later, the reaction mixture was stirred at room temperature for another 2 h after addition of NaOH (100 mmol). When the reaction was completed, as indicated by TLC detection, the pH was adjusted to 6.0 with 1 M HCl. Finally, the precipitate was filtered and washed by water, and then was redissolved in EtOAc and evaporated under reduced pressure to give the product in a yield of 81% as a white solid. mp 185-187 °C. MS (EI) m/z: 255.08 (M)+. 1H NMR (600 MHz, DMSO-d6): δ 12.30 (s, 1H), 10.27 (s, 1H), 8.68 (d, J = 8.4 Hz, 1H), 8.11 (d, J = 7.8 Hz, 1H), 7.85 (d, J = 7.8 Hz, 2H), 7.66 (t, J = 7.8 Hz, 1H), 7.23 (t, J = 7.2 Hz, 1H), 6.94 (d, J = 8.4 Hz, 2H), 2.70 (s, 3H).

Reference： [1]Peng, Da-Yong; Sun, Qi; Zhu, Xiao-Lei; Lin, Hong-Yan; Chen, Qiong; Yu, Ning-Xi; Yang, Wen-Chao; Yang, Guang-Fu [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 22, p. 6739 - 6750]

27
[ 2345-34-8 ]
[ 481-72-1 ]
(1,8-dihydroxy-9,10-dioxo-9,10-dihydroanthracen-3-yl)methyl 4-acetoxybenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-acetyloxy-benzoic acid With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 0.0833333h; Stage #2: 1,8-dihydroxy-3-hydroxymethyl-9,10-anthracenedione In dichloromethane at 20℃;	General procedure for synthesis of ester derivatives of aloe-emodin General procedure: Substituted benzoic acids or cinnamic acids (0.1 mmol) in dry CH2Cl2 (0.2 mL) were treated with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI, 20.6 mg, 0.1 mmol) and DMAP (1.0 mg, 0.006 mmol). The mixtures were stirred at room temperature for 5 min. Aloe-emodin (2, 5.4 mg, 0.02 mmol) was added, and stirring was continued at room temperature until the starting compound was consumed. The resulting solution was diluted with EtOAc (10 mL) and concentrated on a rotary evaporator. The final benzoate and cinnamate derivatives of aloe-emodin were purifiedby using preparative TLC (silica gel, 500 m; hexane/EtOAc, 4:1).

Reference： [1]Dai, Yumin; Harinantenaina, Liva; Bowman, Jessica D.; Da Fonseca, Isabel Osorio; Brodie, Peggy J.; Goetz, Michael; Cassera, Maria B.; Kingston, David G.I. [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 1, p. 269 - 276]

28
[ 2345-34-8 ]
[ 1708-40-3 ]
[ 1528768-70-8 ]

Yield	Reaction Conditions	Operation in experiment
77%	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine In dichloromethane at 20℃; for 72h;	A.b; 1 General procedure: b) The general procedure for HBTU coupling (Procedure 1) was followed, using 4- acetoxybenzoic acid (5.245 g, 29.1 mmol), triethylamine (16 ml_, 1 15.0 mmol), HBTU (1 1.500 g, 30.3 mmol) and 1 ,3-O-benzylidene glycerol (6.305 g, 34.9 mmol) in anhydrous dichloromethane (120 ml_). The crude mixture was passed through a thin layer of silica gel to give 2-phenyl-1 ,3-dioxan-5-yl 4-acetoxybenzoate in 77% yield as a white solid. ESI-MS: M+Na+=365.1. 1H NMR (400 MHz, CDCI3): δ (ppm) 8.19 (d, 2H), 7.40 ~ 7.49 (m, 5H), 7.17 (m, 2H), 5.61 (s, 1 H), 4.41 (m, 1 H), 4.3-4.1 (m, 4H), 2.31 (s, 3H). 13C NMR (50 MHz, CDCI3) δ 168.76, 165.52, 154.55, 137.93, 131.51 , 129.12, 128.32, 128.27, 126.08, 121.63, 101.34, 69.07, 66.56, 21.1 1. Procedure 1 : General Procedure for HBTU Coupling To a stirring suspension of carboxylic acid (1.0 eq.) in anhydrous DCM, HBTU (~1.2 eq.), the alcohol/glycerol derivative (-1.6 eq.) and triethylamine (-4.3 eq.) are added successively. The mixture is stirred at room temperature for 3 days, with the exclusion of light, or until the reaction is complete. The reaction mixture is washed with sat. NaHC03, follow by 0.1 M HCI and brine. The organic phase is then dried over Na2S04, filtered, concentrated and dried in vacuo.

Reference： [1]Current Patent Assignee: POLYACTIVA; ASHA MARINA DSOUZA - WO2014/33, 2014, A1 Location in patent: Page/Page column 115-117

29
[ 2345-34-8 ]
[ 20876-99-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: oxalyl dichloride / 4 h / 20 °C 2: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 3 h / 20 °C 3: potassium carbonate / methanol / 5 h / 20 °C
	Multi-step reaction with 3 steps 1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 4 h / 20 °C 2: N-ethyl-N,N-diisopropylamine / tetrahydrofuran; dichloromethane / 3 h / 20 °C 3: potassium carbonate / methanol / 5 h / 20 °C

Reference： [1]Current Patent Assignee: SPHAERA PHARMA - WO2014/16849, 2014, A2
[2]Dugar, Sundeep; Hollinger, Frank P.; Mahajan, Dinesh; Sen, Somdutta; Kuila, Bilash; Arora, Reena; Pawar, Yogesh; Shinde, Vaibhav; Rahinj, Mahesh; Kapoor, Kamal K.; Bhumkar, Rahul; Rai, Santosh; Kulkarni, Rakesh [ACS Medicinal Chemistry Letters, 2015, vol. 6, # 12, p. 1190 - 1194]

30
[ 122186-40-7 ]
[ 2345-34-8 ]
[ 1590385-31-1 ]

Yield	Reaction Conditions	Operation in experiment
53%	With pyridine In chloroform at 20℃; for 24h;	1 3.5. Acylation of glycoside 2, 3, and 4. General method General procedure: To a solution of glycoside 2,3, or 4 (0.2mmol) in 1mL CHCl3, 0.22mmol of acyl chloride and 0.26mmol of pyridine were added. The reaction mixture was kept at room temperature for 24h and diluted with 20mL CHCl3. The solution was washed with 0.1M H2SO4, satd Na2CO3, water, dried over Na2SO4 and evaporated. The residue was recrystallized from ethanol. 3.5.1 2-(2,3,4,6-Tetra-O-acetyl-β-d-glucopyranosyloxy)-benzyl (4-acetoxy) benzoate (7) The compound 7 was obtained from 4-acetoxy benzoic acid and glycoside 3. Yield 53%, mp 135-137°C. UV λmax (EtOH)/nm: 235. IR (KBr, νmax/cm-1): 1740, 1730, 1600, 1370, 1210, 1040, 910, 750. 1H NMR (CDCl3, 300MHz) δ: 2.03, 2.04, 2.05, 2.07, 2.31 (s, 5×3H, Ac), 3.84-3.88 (m, 1, -5′), 4.16 (dd, 1, J=2.1, 12,3Hz, -6′b), 4.25 (dd, 1, J=5.1, 12.3Hz, H-6′a), 5.11 (d, 1, J=7.2Hz H-1′), 5.15 (m, 1, H-4′), 5.25-5.44 (m, 2, H-2′, -3′), 5.30 (m, 2H, H-7), 7.11 (m, 2H, H-2, H-4), 7.16 (d, 2, J=8.4Hz, -11, H-13), 7.29 (m, 1H, H-3), 7.40 (d, 1H, J=7.2Hz, H-5), 8.09 (d, 2, J=8.4Hz, -10, H-14). 13C NMR (CDCl3, 75.5MHz) δ: 20.6, 21.2 (5×C3, Ac), 61.5 (C2, C6′), 61.9 (CH2, C-7), 68.4 (C, C-4′), 71.1 (C, C-2′), 72.1 (C, C-3′), 72.7 (C, C-5′), 99.4 (C, C-1′), 116.0 (CH, C-2), 121.7 (2×C, C-11, C-13), 123.6 (CH, C-4), 126.4 (C, C-6), 127.7 (C, C-9), 129.3 (C, C-3), 129.4 (C, C-5), 131.3 (2×CH, C-10, C-14), 154.4 (C, C-1), 154.5 (C, C-12), 165.4 (C=O, C-8), 168.8, 169.4, 170.2, 170.5 (5×C=O, Ac). Anal. Calcd for C30H32O14: C, 58.44; H, 5.23. Found: C, 58.31; H, 5.39.

Reference： [1]Stepanova, Elena V.; Belyanin, Maxim L.; Filimonov, Victor D. [Carbohydrate Research, 2014, vol. 388, # 1, p. 105 - 111]

31
[ 2345-34-8 ]
[ 866751-49-7 ]
[ 1128046-28-5 ]

Yield	Reaction Conditions	Operation in experiment
54%	Stage #1: 4-acetyloxy-benzoic acid With benzotriazol-1-ol; dicyclohexyl-carbodiimide In tetrahydrofuran at 0℃; for 5h; Stage #2: 1‐(3,5,6‐trimethylpyrazin‐2‐yl)methanamine In tetrahydrofuran at 20℃;	General Procedure for the Preparation of LigustrazinylAmides (8m-8u, Method B in Scheme 1). Example of (E)-3-(2,5-dimethoxyphenyl)-N-((3,5,6-trimethylpyr-azin-2-yl) methyl) Acrylamide (8m) General procedure: A mixture of 2,5-dimethoxylcinnamic acid (1.04 g, 0.005 mol), HOBt (0.73 g, 0.0055 mol) and DCC (1.12 g, 0.0055 mol) in anhydrous THF (20 mL) was stirred at 0 °C for 5 h, and then the solids were filtered off. A solution of 2-aminemethyl-3,5,6-trimethylpyrazine (7) (0.755 g, 0.005 mol) in anhydrous THF (15 mL) was then added to the filtrate. After the mixture was stirred at room temperature overnight, the solvent was evaporated in vacuo and the residue was poured into ethyl acetate and washed with saturated sodium bicarbonate, 50% citric acid and brine. The organic layer was dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude product was purified by recrystallisation from 90-95% ethanol.

Reference： [1]Li, Zhenyu; Yu, Fang; Cui, Lei; Chen, Wenmin; Wang, Shouxun; Zhan, Peng; Shen, Yuemao; Liu, Xinyong [Medicinal Chemistry, 2014, vol. 10, # 1, p. 81 - 89]

32
[ 2345-34-8 ]
[ 1610615-93-4 ]
C₃₄H₄₀O₁₉ [ No CAS ]
C₄₃H₄₆O₂₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 53% 2: 14%	With di-isopropyl azodicarboxylate; triphenylphosphine In N,N-dimethyl-formamide at 0 - 75℃; for 0.5h;	β-D-[3-O-(4-Acetyl-3,5-dimethoxycinnamoyl)]-fructofuranosyl-α-D-[6-O-(4-acetyl-benzoyl)]-glucopyranoside (12) and β-D-[3-O-(4-acetyl-3,5-dimethoxycinnamoyl)-6-O-(4-acetylbenzoyl)]-fructofuranosyl-α-D-[6-O-(4-acetyl-benzoyl)]-glucopyranoside(13) Compound 6 (1.18 g, 2 mmol) was dissolved in DMF (20 mL) bystirring at 60 C. The mixture was cooled to room temperaturebefore the addition of triphenylphosphine (1.42 g, 5.4 mmol), 5(0.90 g, 5.0 mmol), and DMF (6 mL). After complete dissolution, themixture was cooled to 0 C and DIAD (2.09 g, 5.4 mmol) was added.The obtained mixture was stirred for 0.5 h at 75 C and DMF wasremoved under diminished pressure at 50 C. The crude residuewas then purified by reverse column chromatography (methanol/water/acetate, 1:1:0.001) to afford 12 (0.80 g, 53%) and 13 (0.26 g,14%). Data for compound 12: mp 132e134 C. [a]D25 12.5 (c 0.97,MeOH).1H NMR (500 MHz, CD3OD): d8.08 (dd, J9, 2 Hz, 2H), 7.73(d, J16 Hz, 1H), 7.21 (dd, J9, 2 Hz, 2H), 6.99 (s, 2H), 6.60 (d,J16 Hz, 1H), 5.50 (d, J3.5 Hz, 1H), 5.50 (d, J7.5 Hz, 1H), 4.73 (dd,J12, 2 Hz, 1H), 4.46 (dd, J12, 5 Hz, 1H), 4.38 (m, 1H), 4.27 (ddd,J10, 5, 2 Hz, 1H), 3.93 (m, 1H), 3.84 (s, 6H), 3.79 (m, 1H), 3.70 (m,2H), 3.63 (m, 2H), 3.47 (m, 2H), 2.29 (s, 3H), 2.26 (s, 3H) ppm. 13CNMR (125 MHz, CD3OD): d170.7 (2C), 167.7, 167.4, 156.3, 154.0(2C), 147.0, 134.2, 132.4 (2C), 131.9, 128.8, 123.2 (2C), 119.0, 106.3(2C), 105.0, 93.3, 84.3, 79.9, 75.0, 74.2, 73.2, 72.6, 71.8, 65.8, 65.7,63.5, 57.0 (2C), 21.0, 20.3 ppm. HRMS (ESI): calcd for C34H40O19Na[MNa] 775.2061; found 775.2069. Data for compound 13: mp128e130 C. [a]D25 1.1 (c 0.94, MeOH). 1H NMR (500 MHz, CD3OD):d8.08 (d, J7.5 Hz, 2H), 8.03 (d, J7.5 Hz, 2H), 7.74 (d, J16 Hz, 1H),7.15 (d, J8.5 Hz, 2H), 7.14 (d, J8.5 Hz, 2H), 6.98 (s, 2H), 6.60 (d,J16 Hz, 1H), 5.57 (d, J3.5 Hz, 1H), 5.54 (d, J7.5 Hz, 1H), 4.58 (m,3H), 4.38 (dd, J12, 5 Hz, 1H), 4.31 (m, 1H), 4.21 (dd, J12, 5 Hz, 1H),3.83 (s, 6H), 3.67 (m, 3H), 3.40 (m, 3H), 2.27 (s, 3H), 2.26 (s,6H) ppm. 13C NMR (125 MHz, CD3OD): d170.7 (2C), 170.4, 167.6,167.5, 167.1, 156.2 (2C), 154.0 (2C), 147.2, 134.2, 132.4 (4C), 131.9,128.8, 128.7, 123.2 (2C), 123.0 (2C), 118.8, 106.3 (2C), 105.0, 93.0,81.6, 79.5, 75.0, 74.8, 73,2, 72.6, 72.0, 66.3, 65.9, 65.8, 57.0 (2C), 21.1(2C), 20.4 ppm. HRMS (ESI): calcd for C43H46O22Na [MNa]937.2378; found 937.2373.
1: 48% 2: 19%	With di-isopropyl azodicarboxylate; triphenylphosphine In N,N-dimethyl-formamide at 0 - 75℃; for 0.5h;	β-D-[3-O-(4-Acetyl-3,5-dimethoxycinnamoyl)]-fructofuranosyl-α-D-[6-O-(4-acetyl-benzoyl)]-glucopyranoside (12) and β-D-[3-O-(4-acetyl-3,5-dimethoxycinnamoyl)-6-O-(4-acetylbenzoyl)]-fructofuranosyl-α-D-[6-O-(4-acetyl-benzoyl)]-glucopyranoside(13) Compound 6 (1.18 g, 2 mmol) was dissolved in DMF (20 mL) bystirring at 60 C. The mixture was cooled to room temperaturebefore the addition of triphenylphosphine (1.42 g, 5.4 mmol), 5(0.90 g, 5.0 mmol), and DMF (6 mL). After complete dissolution, themixture was cooled to 0 C and DIAD (2.09 g, 5.4 mmol) was added.The obtained mixture was stirred for 0.5 h at 75 C and DMF wasremoved under diminished pressure at 50 C. The crude residuewas then purified by reverse column chromatography (methanol/water/acetate, 1:1:0.001) to afford 12 (0.80 g, 53%) and 13 (0.26 g,14%). Data for compound 12: mp 132e134 C. [a]D25 12.5 (c 0.97,MeOH).1H NMR (500 MHz, CD3OD): d8.08 (dd, J9, 2 Hz, 2H), 7.73(d, J16 Hz, 1H), 7.21 (dd, J9, 2 Hz, 2H), 6.99 (s, 2H), 6.60 (d,J16 Hz, 1H), 5.50 (d, J3.5 Hz, 1H), 5.50 (d, J7.5 Hz, 1H), 4.73 (dd,J12, 2 Hz, 1H), 4.46 (dd, J12, 5 Hz, 1H), 4.38 (m, 1H), 4.27 (ddd,J10, 5, 2 Hz, 1H), 3.93 (m, 1H), 3.84 (s, 6H), 3.79 (m, 1H), 3.70 (m,2H), 3.63 (m, 2H), 3.47 (m, 2H), 2.29 (s, 3H), 2.26 (s, 3H) ppm. 13CNMR (125 MHz, CD3OD): d170.7 (2C), 167.7, 167.4, 156.3, 154.0(2C), 147.0, 134.2, 132.4 (2C), 131.9, 128.8, 123.2 (2C), 119.0, 106.3(2C), 105.0, 93.3, 84.3, 79.9, 75.0, 74.2, 73.2, 72.6, 71.8, 65.8, 65.7,63.5, 57.0 (2C), 21.0, 20.3 ppm. HRMS (ESI): calcd for C34H40O19Na[MNa] 775.2061; found 775.2069. Data for compound 13: mp128e130 C. [a]D25 1.1 (c 0.94, MeOH). 1H NMR (500 MHz, CD3OD):d8.08 (d, J7.5 Hz, 2H), 8.03 (d, J7.5 Hz, 2H), 7.74 (d, J16 Hz, 1H),7.15 (d, J8.5 Hz, 2H), 7.14 (d, J8.5 Hz, 2H), 6.98 (s, 2H), 6.60 (d,J16 Hz, 1H), 5.57 (d, J3.5 Hz, 1H), 5.54 (d, J7.5 Hz, 1H), 4.58 (m,3H), 4.38 (dd, J12, 5 Hz, 1H), 4.31 (m, 1H), 4.21 (dd, J12, 5 Hz, 1H),3.83 (s, 6H), 3.67 (m, 3H), 3.40 (m, 3H), 2.27 (s, 3H), 2.26 (s,6H) ppm. 13C NMR (125 MHz, CD3OD): d170.7 (2C), 170.4, 167.6,167.5, 167.1, 156.2 (2C), 154.0 (2C), 147.2, 134.2, 132.4 (4C), 131.9,128.8, 128.7, 123.2 (2C), 123.0 (2C), 118.8, 106.3 (2C), 105.0, 93.0,81.6, 79.5, 75.0, 74.8, 73,2, 72.6, 72.0, 66.3, 65.9, 65.8, 57.0 (2C), 21.1(2C), 20.4 ppm. HRMS (ESI): calcd for C43H46O22Na [MNa]937.2378; found 937.2373.

Reference： [1]Wu, Yongjiang; Shi, Qiyuan; Lei, Houliang; Liu, Xuesong; Luan, Lianjun [Tetrahedron, 2014, vol. 70, # 24, p. 3757 - 3761]
[2]Wu, Yongjiang; Shi, Qiyuan; Lei, Houliang; Liu, Xuesong; Luan, Lianjun [Tetrahedron, 2014, vol. 70, # 24, p. 3757 - 3761]

33
[ 2345-34-8 ]
[ 883535-89-5 ]
[ 1616960-59-8 ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 6.0h;	General procedure: A solution of <strong>[883535-89-5]2-(2-methyl-1H-indol-1-yl)ethanamine</strong> (4a) (65 mg, 0.373 mmol) and 4-(piperidin-1-yl)benzoic acid (5) (76 mg, 1 eq.), and dimethylaminopyridine (catalytic, ?5 mg) in dichloromethane (6 mL) was added 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide.hydrochloride (EDCI) (92 mg, 1.3 eq.) at room temperature. The resulting reaction mixture was stirred for 6h. At the conclusion of the reaction (TLC), water (15 mL) was added to quench the reaction. The product was extracted with ethyl acetate (20mL×3). Organics were washed with dilute HCl (10 mL), saturated NaHCO3 solution (10 mL), water (10 mL) and brine solution (10 mL) and dried over Na2SO4 and concentrated. The resulting crude product was subjected to silica gel chromatography eluting with 0-40% ethyl acetate in hexane to furnish 7k (TG7-152) (100mg, 74% yield). 1H NMR (CDCl3): delta 7.52 (d, J=5.6Hz, 1H), 7.49 (d, J=8.8Hz, 2H), 7.30 (d, J=8Hz, 1H), 7.07 (m, 2H), 6.80 (d, J=8.2Hz, 2H), 6.23 (s, 1H), 5.98 (t, J=5.4Hz, 1H), 4.33 (t, J=6Hz, 2H), 3.76 (q, J=6Hz, 2H), 3.25 (t, J=4.8Hz, 4H), 2.37 (s, 3H), 1.6 (m, 6H). LCMS (ESI): >97% purity at lambda 254, MS; m/z, 362 [M+H]+. Anal. Calcd. for C23H27N3O: C, 76.42; H, 7.53; N, 11.62; found; C, 76.48; H, 7.55; N, 11.59.

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 82,p. 521 - 535

34
[ 432027-96-8 ]
[ 2345-34-8 ]
2-(prop-2-yn-1-yl)pent-4-yn-1-yl 4-hydroxybenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap / dichloromethane / 46 h / 0 - 20 °C 2: ammonium acetate; water / methanol / 76 h / 20 °C

Reference： [1]Current Patent Assignee: POLYACTIVA - WO2014/134689, 2014, A1

35
[ 432027-96-8 ]
[ 2345-34-8 ]
2-(prop-2-yn-1-yl)pent-4-yn-1-yl 4-acetoxybenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃; for 46h;	3 Example 3: 2-(prop-2-yn-1-yl)pent-4-yn-1-yl 4-hydroxybenzoate [41 1] Example 3: 2-(Pro -yl 4-hydroxybenzoate [412] To a solution of 2-(prop-2-yn-1-yl)pent-4-yn-1 -ol (J. Org. Chem. 2002, 67, 2778) (380 mg, 3.1 1 mmol), 4-acetoxybenzoic acid (619 mg, 3.43 mmol) and DMAP (36.9 mg, 0.30 mmol) in DCM at 0°C was added EDC HCI (663 mg, 3.46 mmol) and the resulting solution stirred at 0°C for 1h before allowing to warm to rt. The mixture was stirred for an additional 21 h before further EDC HCI (652 mg, 3.40 mmol) was added. The resultant mixture was stirred at rt for an additional 24h before Et20 and H20 were added. The product was extracted (Et20), washed (H20, then brine), dried (Na2S04), filtered and concentrated under reduced pressure. Flash chromatography (0 - 100% EtOAc / petrol gradient elution) gave 2-(prop-2-yn-1-yl)pent-4-yn-1-yl 4-acetoxybenzoate (427 mg, 1.50 mmol, 48%) as a colourless oil. 2-(prop-2-yn-1-yl)pent-4-yn-1-yl 4-acetoxybenzoate (423.3 mg, 1.49 mmol) was dissolved in a 3:1 mixture of MeOH:H20 (16 mL) before NH4OAc (583.6 mg, 7.57 mmol) was added. The resultant mixture was stirred at rt for 76 h before EtOAc and H20 were added. The product was extracted (EtOAc), washed (H20, then brine), dried (Na2S04), filtered and concentrated under reduced pressure. Flash chromatography (0 - 100% EtOAc / petrol gradient elution) gave the title compound (295.1 mg, 1.22 mmol, 82%) as a white solid. ESI-MS: m/z 243 ([M+Hf). 1H NMR (400 MHz CDCI3): δ 7.95 (m, 2H), 6.86 (m, 2H), 4.38 (d, J = 6.1 Hz, 2H), 2.47 (dd, J = 6.2, 2.7 Hz, 4H), 2.28 (m, 1 H), 2.03 (t, J = 2.7 Hz, 2H).

Reference： [1]Current Patent Assignee: POLYACTIVA - WO2014/134689, 2014, A1 Location in patent: Paragraph 411-412

36
[ 2345-34-8 ]
[ 110-82-7 ]
[ 1383677-48-2 ]

Yield	Reaction Conditions	Operation in experiment
65%	With tert.-butylhydroperoxide; (6,8,15,17-tetramethyldibenzo[b,i][1,4,8,11]tetraazacyclotetradecinato)copper(II) In neat (no solvent) at 80℃; for 24h; Schlenk technique; Inert atmosphere;	4.4. General procedures for dehydrogenative functionalization of alkanes toallylic esters (in absence of added solvent) General procedure: Under an argon atmosphere, [Cu(MeTAA)] (2.0 mg, 0.005 mmol)and benzoic acid (61 mg, 0.5 mmol) were added in an oven-dried Schlenk tube containing a magnetic stir bar. The Schlenk tube wasevacuated and back filled with argon (3 cycles). Subsequently1.50 mmol (3.0 equiv) of TBHP and 1.0 mL cyclohexane were injected to the Schlenk tube via a syringe. Then the Schlenk tube was placed intoan oil bath and heated at 80 °C for 24 h. Once the reaction was completed,the reaction mixture was concentrated in vacuum and the residuewas dissolved in dichloromethane and purified by column chromatographyusing silica and hexane was used as eluent.
72 %Spectr.	With di-tert-butyl peroxide; [(bis(2-pyridylimino)isoindole)Cu(PPh₃)₂] In acetonitrile; benzene at 100℃; for 24h; Inert atmosphere; Sealed tube;

Reference： [1]Mondal, Rakesh; Chakraborty, Gargi; van Vliet, Kaj M.; van Leest, Nicolaas P.; de Bruin, Bas; Paul, Nanda D. [Inorganica Chimica Acta, 2020, vol. 500]
[2]Tran, Ba L.; Driess, Matthias; Hartwig, John F. [Journal of the American Chemical Society, 2015, vol. 136, # 49, p. 17292 - 17301]

37
[ 6309-46-2 ]
[ 2345-34-8 ]

Yield	Reaction Conditions	Operation in experiment
84%	With oxygen In water; <i>tert</i>-butyl alcohol at 120℃; for 0.533333h; Flow reactor; Green chemistry;

Reference： [1]Osako, Takao; Torii, Kaoru; Uozumi, Yasuhiro [RSC Advances, 2015, vol. 5, # 4, p. 2647 - 2654]

38
[ 2345-34-8 ]
[ 333-20-0 ]
4-(isothiocyanatocarbonyl)phenyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: 4-acetyloxy-benzoic acid With trichloroisocyanuric acid; triphenylphosphine In toluene at 0℃; for 0.25h; Stage #2: potassium thioacyanate In toluene at 0 - 20℃; for 1.5h;	Preparation of Benzoyl Isothiocyanate from Benzoic Acid General procedure: To a cold solution of triphenylphosphine (0.262 g, 1 mmol) in toluene (3 mL), trichloroisocyanuric acid (0.069 g, 0.3 mmol) was added with continuous stirring. Benzoic acid (0.097 g, 0.8 mmol) was added and stirring was continued for 15 min. Potassium thiocyanate (0.193 g, 2 mmol) was added and the temperature was raised up to room temperature. Stirring was continued for 40 min at room temperature. The progress of the reaction was followed by TLC. Upon completion of the reaction, the concentrated residue passed through a short silica gel column using n-hexane / ethyl acetate mixture (vol. ratio: 60:1) as the eluent. Benzoyl isothiocyanate was obtained with 95 % yield after removing the solvent under reduced pressure.

Reference： [1]Entezari, Najmeh; Akhlaghinia, Batool; Rouhi-Saadabad, Hamed [Croatica Chemica Acta, 2014, vol. 87, # 3, p. 201 - 206]

39
[ 2345-34-8 ]
[ 33513-42-7 ]
[ 20877-09-2 ]

Yield	Reaction Conditions	Operation in experiment
75%	With di-tert-butyl peroxide; copper(II) bis(trifluoromethanesulfonate) In 1,2-dichloro-ethane at 130℃; for 12h; Sealed tube;	General procedure for the amidation of benzoic acids: General procedure: A 50 mL sealed tube (with a Teflon high pressure valve) equipped with a magnetic stir bar was charged with Cu(OTf)2 (0.05 mmol), followed by carboxylic acid (0.5 mmol), formamide (2.0 mmol), tert-butyl peroxide (DTBP, 1 mmol), and DCE (1 mL). After the reaction mixture was stirred at 130 °C for 12 h, it was allowed to cool to ambient temperature. The reaction mixture was diluted with ethyl acetate, and then filtered through a small pad of Celite. The filtrate was washed with saturated aqueous NaHCO3 (5 mL) and brine (5 mL, twice). The organic phase was dried (Na2SO4) and concentrated in vacuo. The residue was purified by silica gel preparative TLC to give the corresponding product.

Reference： [1]Liu, Hong-Qiang; Liu, Jun; Zhang, Yang-Hui; Shao, Chang-Dong; Yu, Jing-Xun [Chinese Chemical Letters, 2015, vol. 26, # 1, p. 11 - 14]

40
[ 2345-34-8 ]
n-butyl 5-hydroxyanthranilate [ No CAS ]
n-butyl 5-hydroxy-N-(40-acetoxybenzoyl)anthranilate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	Stage #1: 4-acetyloxy-benzoic acid With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 20℃; for 6h; Stage #2: n-butyl 5-hydroxyanthranilate In N,N-dimethyl-formamide at 20℃; for 12h;	n-Butyl 5-hydroxy-N-(40-acetoxybenzoyl)anthranilate(15) Hydroxybenzoic acid (1 g, 7.25 mmol) was reacted with acetic anhydride (40 mL) in the presence of a catalytic amount of phosphoric acid at 60 °C for 1 h. The reaction mixture was added with cold water to form the precipitate which was filtered and washed with water to yield 4-acetoxybenzoic acid (14, 500 mg, 2.78 mmol) as a white powder. Compound 14 was dissolved in N,N-dimethylformamide (10 mL) and added with EDCI (636 mg, 3.32 mmol) at room temperature for 6 h. To this mixture was added 5-hydroxyanthranilic acid butyl ester (7, 524 mg, 2.5 mmol) and stirred at room temperature for 12 h. The reaction mixture was added with water andextracted with dichloromethane and resulting organic extracts were dried with anhydrous MgSO4 and filtered, and the filtratewas concentrated to yield crude compound which was purifiedby column chromatography (ethyl acetate/n-hexane = 1:3) toafford 15 as a white powder. Yield: 362 mg (39 %); m.p.:180-181 C; 1H NMR (400 MHz, CDCl3) d: 0.99 (3H, t,J = 7.6 Hz,OCH2CH2CH2CH3), 1.49 (2H, quit, J = 7.2 Hz,OCH2CH2CH2CH3), 1.76 (2H, sext, J = 7.2 Hz, OCH2CH2CH2CH3), 2.34 (3H, s, OCOCH3), 4.34 (2H, t,J = 6.4 Hz, OCH2CH2CH2CH3), 5.53 (1H, br s, OH), 7.10(1H, dd, J = 2.8, 8.8 Hz, H-4), 7.23 (2H, d, J = 8.4 Hz,H-30,50), 7.53 (1H, d, J = 2.8 Hz, H-6), 8.34 (2H, d,J = 8.4 Hz, H-20,60), 8.76 (1H, d, J = 8.8 Hz, H-3), 11.83(1H, s, NHCO); 13C NMR (100 MHz, CDCl3) d: 13.7(OCH2CH2CH2CH3), 19.2 (OCH2CH2CH2CH3), 21.2(OCOCH3), 30.6 (OCH2CH2CH2CH3), 65.5 (OCH2CH2-CH2CH3), 116.8 (C-1), 116.9 (C-6), 121.9 (C-30,50), 122.2 (C-3), 128.8 (C-20,60), 132.5 (C-10), 135.2 (C-2), 150.9 (C-5),153.4 (C-40), 164.5 (COO), 168.2 (NHCO), 169.1 (OCOCH3);GC-MS (EI) m/z: 371 [M]?.

Reference： [1]Kim, Sohee; Shin, Beom Soo; Ma, Eunsook [Archives of Pharmacal Research, 2015, vol. 38, # 6, p. 1147 - 1156]

41
[ 2345-34-8 ]
isosorbide mononitrate [ No CAS ]
(1S,4S,5R,8R)-8-nitrooxy-2,6-dioxabicyclo[3.3.0]octan-4-yl-4-acetoxybenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With dimethylallyl diphosphate; dicyclohexyl-carbodiimide In tetrahydrofuran at 0 - 20℃; for 5h;	Drugs and Chemicals General procedure: The formulae of NO donor compounds and their general synthesis processes were listed in Fig. 1. Briefly, acetyl acid (compounds 1-6, 10 mmol), isosorbide mononitrate (1.91 g, 10 mmol, CAS No. 16051-77-7, [α]D=168° (c=1.0, ethanol (EtOH))) and dimethylallylpyrophosphate (DMAP) (0.24 g, 1 mmol) were dissolved in 100 mL dry tetrahydrofuran (THF), then dicyclohexylcarbodiimide (DCC) (4.12 g, 10 mmol) was added to the solution at 0°C. The mixture was stirred at room temperature for 5 h. The resulting mixture was filtered and concentrated in vacuo. The crude product was purified by column chromatography over silica gel using ethyl acetate-n-hexane (7 : 3) as eluent. The compounds A-F (83-88% yield) was obtained as white powder. The structures of NO donor compounds were determined by IR, MS, and NMR. Column chromatography was carried out with silica gel 60 Merck for purification, and the purity of NO donor compounds was 99%. Stock solution of NO donor compounds (25 mM) was prepared with dimethyl sulfoxide(DMSO) and stored at -20 °C for in vitro test. The stock solution was further diluted with the appropriate assay medium immediately before use. While in vivo test AFIM was prepared with physiological saline before use. ACZ included as a positive control was purchased from Sigma-Aldrich (St. Louis, MO, U.S.A.). The measurement kits for lactate dehydrogenase (LDH), Lactic acid (LAC), bicinchoninic acid (BCA) protein assay, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and ATPase activities assay kits were obtained from Nanjing Jiancheng Bioengineering Institute (Nanjing, China).

Reference： [1]Fan, Peng-Cheng; Ma, Hui-Ping; Jiang, We I; Li, Lin; Ren, Jun; Jing, Lin-Lin; Jia, Zheng-Ping [Biological and Pharmaceutical Bulletin, 2015, vol. 38, # 9, p. 1280 - 1289]

42
C₂₅H₂₆O₄Si [ No CAS ]
[ 2345-34-8 ]

Yield	Reaction Conditions	Operation in experiment
84%	With water; N,N-dimethyl-formamide at 45℃; for 12h; Green chemistry; chemoselective reaction;	General procedure General procedure: A solution of the silyl ester (1 mmol) in DMF-H2O (20:1) (5 mL) was heated to 70 °C, and stirred for 1-2 h (or until all starting material has been consumed). The reaction was cooled to rt, diluted with ether (20 mL), washed successively with sat. aq. NH4Cl and brine, dried (Na2SO4), and concentrated under reduced pressure. The residue was purified by silica gel flash column chromatography

Reference： [1]Chen, Bo; Sun, Hui-Xia; Qin, Jian-Feng; Wang, Bing [Tetrahedron Letters, 2016, vol. 57, # 3, p. 253 - 255]

43
[ 2345-34-8 ]
(S)-N1-(14-amino-3-methyl-6,9,12-trioxa-3-azatetradecyl)-N3-(4-(diethylamino)-2-(4-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenyl)-N1-methylisophthalamide tetrahydrochloride [ No CAS ]
(S)-4-(1-(3-(4-(diethylamino)-2-(4-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenylcarbamoyl)phenyl)-2,5-dimethyl-1-oxo-8,11,14-trioxa-2,5-diazahexadecan-16-ylcarbamoyl)phenyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	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 20℃; for 2h;	345 Example 345 DIEA (0.11 mL, 0.654 mmol) was added to (S)-N1-(14-amino-3-methyl-6,9,12-trioxa-3-azatetradecyl)-N3-(4-(diethylamino)-2-(4-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenyl)-N1-methylisophthalamide tetrahydrochloride 340a (0.101 g, 0.106 mmol), 4-acetoxybenzoic acid (19.1 mg, 0.106 mmol) and HATU (48 mg, 0.127 mmol) in DMF (2 mL) and the mixture stirred for 2 hours at room temperature. The reaction was diluted with ethyl acetate, washed with water and brine, dried (MgSO4) and evaporated. The residue was purified by PTLC (10% methanol/20% ethyl acetate/dichloromethane) to give the intermediate (S)-4-(1-(3-(4-(diethylamino)-2-(4-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenylcarbamoyl)phenyl)-2,5-dimethyl-1-oxo-8,11,14-trioxa-2,5-diazahexadecan-16-ylcarbamoyl)phenyl acetate as a yellow foam (0.082 g, 75%); MS (ES, m/z): 972 [M+H]+. Ammonia in methanol (2M, 4 mL) was added and the mixture stirred overnight at room temperature. The reaction was evaporated and the residue purified by PTLC (10% methanol/20% ethyl acetate/dichloromethane) to give product as a yellow foam (0.065 g, 83%);

Reference： [1]Current Patent Assignee: ARDELYX, INC. - US9301951, 2016, B2 Location in patent: Page/Page column 619; 620

44
[ 2345-34-8 ]
[ 52568-28-2 ]
3-oxo-2-(2-(pyridin-2-yl)propan-2-yl)-2,3-dihydrobenzo[d]isothiazol-6-yl acetate [ No CAS ]

Reference： [1]Organic Letters,2014,vol. 16,p. 5644 - 5647

45
[ 2345-34-8 ]
[ 52568-28-2 ]
4-((2-(pyridin-2-yl)propan-2-yl)carbamoyl)phenyl acetate [ No CAS ]

Reference： [1]Organic Letters,2014,vol. 16,p. 5644 - 5647

46
[ 2345-34-8 ]
[ 501-65-5 ]
C₂₂H₁₈O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With [bis(acetato)-(η-p-cymene)-ruthenium] In 1,4-dioxane; n-heptane; 1,3,5-trimethyl-benzene at 80℃; for 24h; Inert atmosphere; Sealed tube; stereoselective reaction;	Methods General procedure: The general procedure for decarboxylative alkyne hydroarylation is as follows. In a nitrogen-atmosphere glovebox, [Ru(p-cymene)(OAc)2] (7, 71 mg, 0.2 mmol) and 10.0 ml of mixed solvent (4.0 ml dioxane, 4.0 ml mesitylene and 2.0 ml heptanes) were added into a 20 ml scintillation vial equipped with a magnetic stir bar. The mixture was stirred for ten minutes to be used as a homogeneous stock solution of catalyst precursor. A 4 ml scintillation vial equipped with a magnetic stir bar was charged with the alkyne substrate (0.2 mmol, 1.0 equiv.), arenecarboxylic acid substrate (0.4 mmol) and 1.0 ml of the stock solution of catalyst precursor (containing 0.02 mmol of complex 7). The vial was then sealed with a Teflon-lined cap, transferred out of the glovebox and stirred in an 80 °C oil bath for 24 hours. The reaction mixture was cooled to room temperature and then all volatile materials were removed under reduced pressure. Further purification was achieved by flash column chromatography using dichloromethane, ethyl acetate and hexanes as the eluent. The E/Z alkene stereo- and regioselectivity for aromatic substitution was determined by 1 H NMR spectroscopy of the unpurified reaction mixture. Yields of the isolated products are based on the average of two runs under identical conditions.

Reference： [1]Zhang, Jing; Shrestha, Ruja; Hartwig, John F.; Zhao, Pinjing [Nature Chemistry, 2016, vol. 8, # 12, p. 1144 - 1151]

47
[ 94-13-3 ]
[ 2345-34-8 ]
C₁₉H₁₈O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; dicyclohexyl-carbodiimide; In dichloromethane;	A solution of 4-acetoxybenzoic acid (524.8 g, 2.91 mol), propyl 4-hydroxybenzoate (500 g, 2.78 mol), N, N-dimethylaminopyridine (DMAP) (20.34 g, 0.17 mmol) in dichloromethane (2.51 ml) was added dropwise a solution of N, N-dicyclohexylcarbodiimide (DCC) (601.3 g, 2.91 mol) in dichloromethane (601.3 g). After completion of the dropwise addition, the mixture was stirred overnight, the precipitate was filtered, and the solvent was distilled off. Methanol (3.4 L) was added to and dissolved in the resulting oil, and then a solution of potassium carbonate (446.1 g, 3.23 mol) in water (1.7 L) was slowly added dropwise under cooling. The reaction mixture was stirred for 1 hour, then neutralized with 35% hydrochloric acid (325 mL), the precipitated crystals were filtered and the crude product was dried to give 4-propoxycarbonylphenyl 4-hydroxybenzoate in two steps 72 .9% (602.17 g, 2.00 mol).

Reference： [1]Patent: JP2015/67566,2015,A .Location in patent: Paragraph 0029-0031

48
4-acetoxycinnamic acid amide [ No CAS ]
[ 2345-34-8 ]
[ 99-96-7 ]

Yield	Reaction Conditions	Operation in experiment
1: 59% 2: 36%	Stage #1: 4-acetoxycinnamic acid amide With oxygen; ozone; acetic acid In water at 0 - 10℃; for 2h; Stage #2: With dihydrogen peroxide In water at 15 - 90℃; for 2h;	3 In a 100 mL four-necked flask equipped with a thermometer, a condenser, a stirrer, and an introduction line of an ozone / oxygen mixed gas, 0.51 g (2.5 mmol) of the above-prepared 4-acetoxycinnamic acid amide, 18 g of acetic acid, 2.0 g of water was charged and stirred at 0 to 10 ° C. Oxygen gas having an ozone concentration of 4 to 5% was blown at a rate of about 40 mL / min for about 2 hours. After completion of the reaction, only oxygen was bubbled for 15 minutes or more to remove residual ozone in the system. Thereafter, 1.0 g of 30 to 35% hydrogen peroxide water was added at 15 to 25 ° C., and the mixture was heated at a liquid temperature of 80 to 90 ° C. for 2 hours. After completion of the reaction, the reaction solution was cooled to room temperature and quantitatively analyzed by HPLC to calculate the yieldThe yield of 4-acetoxybenzoic acid is59%, the yield of 4-hydroxybenzoic acid was 36%, and the yield of the objective product obtained by totaling these was 95%.

Reference： [1]Current Patent Assignee: TORAY INDUSTRIES INC - JP2015/168632, 2015, A Location in patent: Paragraph 0073; 0076; 0077; 0078; 0079

49
3-(4-acetoxyphenyl)acrylic acid [ No CAS ]
[ 2345-34-8 ]
[ 99-96-7 ]

Yield	Reaction Conditions	Operation in experiment
1: 51% 2: 30%	Stage #1: 3-(4-acetoxyphenyl)acrylic acid With oxygen; ozone; acetic acid In water at 0 - 10℃; for 1.16667h; Stage #2: With dihydrogen peroxide In water at 15 - 95℃; for 3h;	1 Thermometer, condenser, stirrer,And an introduction line of an ozone / oxygen mixed gas,A 100 mL four-necked flask was charged with 0.49 g (2.4 mmol) of 4-acetoxycinnamic acid,27 g of acetic acid and 3.0 g of water were charged,While stirring at 0 to 10 ° C.,Oxygen gas having an ozone concentration of 4 to 5% was blown at a rate of about 40 mL / min for about 1 hour and 10 minutes. After completion of the reaction,In order to remove residual ozone in the system, only oxygen was aerated for 15 minutes or more Thereafter, at 30 to 35% hydrogen peroxide water at 15 to 25°C. 1.9 g was added,At a liquid temperature of 60 to 70 ° C. After heating for 5 hours, it was heated at a liquid temperature of 85 to 95 ° C. for 2.5 hours After completion of the reaction, the reaction solution was cooled to room temperature and quantitatively analyzed by HPLC to calculate the yield, the yield of 4-acetoxybenzoic acid was 51%, the yield of 4-hydroxybenzoic acid was 30% The total yield of target product was 81%.

Reference： [1]Current Patent Assignee: TORAY INDUSTRIES INC - JP2015/168632, 2015, A Location in patent: Paragraph 0061; 0065; 0066; 0067; 0068

50
[ 2345-34-8 ]
(S)-dibenzyl 2-(2-ethoxy-4-(5-((((R)-2-((R)-1-(N-hydroxyformamido)propyl)heptanamido)methyl)carbamoyl)furan-2-yl)benzamido)succinate [ No CAS ]
(S)-dibenzyl 2-(4-(5-((((R)-2-((R)-1-(N-((4-acetoxybenzoyl)oxy)formamido)propyl)heptanamido)methyl)carbamoyl)furan-2-yl)-2-ethoxybenzamido)succinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	Stage #1: 4-acetyloxy-benzoic acid With 4-methyl-morpholine; HATU In N,N-dimethyl-formamide; acetonitrile at 20℃; for 0.25h; Stage #2: (S)-dibenzyl 2-(2-ethoxy-4-(5-((((R)-2-((R)-1-(N-hydroxyformamido)propyl)heptanamido)methyl)carbamoyl)furan-2-yl)benzamido)succinate In N,N-dimethyl-formamide; acetonitrile at 20℃; for 5h;	148 INTERMEDIATE 148: (S)-dibenzyl 2-(4-(5-((((R)-2-((R)-1-(N-((4- acetoxybenzoyl)oxy)formamido)propyl)heptanamido)methyl)carbamoyl)furan-2-yl)-2- ethoxybenzamido)succinate INTERMEDIATE 148: (S)-dibenzyl 2-(4-(5-((((R)-2-((R)-1-(N-((4- acetoxybenzoyl)oxy)formamido)propyl)heptanamido)methyl)carbamoyl)furan-2-yl)-2- ethoxybenzamido)succinate To a solution containing 4-acetoxybenzoic acid (89 mg, 0.492 mmol) in MeCN (1 ml_) and DMF (1 ml_) was added HATU (281 mg, 0.738 mmol) and N-methylmorpholine (0.135 ml_, 1.230 mmol). The reaction was stirred at RT for 15 min. (S)-dibenzyl 2-(2-ethoxy-4-(5- ((((R)-2-((R)-1 -(N-hydroxyformamido)propyl)heptanamido)methyl)carbamoyl)furan-2- yl)benzamido)succinate (200 mg, 0.246 mmol) was added and stirred at RT for 5 h. Reaction was concentrated diluted with DCM and water (5 ml_ each) and layers were separated. The organic phase was passed through a phase separator and concentrated. Purification by Si (0-100% EtOAc/Hex) afforded the title compound as a colorless solid. (166 mg, 69% yield). MS (m/z) 976.9 (M+H)+

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - WO2017/6296, 2017, A1 Location in patent: Page/Page column 214

51
[ 2345-34-8 ]
2-chloro-4-[(1r,3r)-3-amino-2,2,4,4-tetramethylcyclobutoxy]benzonitrile [ No CAS ]
4-[[(1,3-trans)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl]carbamoyl]phenyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 2h;	1 Step 1 Into a 25-mL round-bottom flask, was placed a solution of 4-(acetyloxy)benzoic acid (100,0 mg, 0.56 mmol, 1.00equiv) in Ν,Ν-dimethylformamide (10 mL), 2-chloro-4-[(1r,3r)-3-amino-2,2,4,4-tetramethylcyclobutoxy]benzonitrile [prepared as described previously by Crew, A.P. et al. in US 20150291562] (190.0 mg, 0.68 mmol, 1.10 equiv), HATU (253.0 g, 665.39 mmol, 1.20 equiv), DIEA (0.5 mL, 5.00 equiv). The resulting solution was stirred for 2 h at room temperature. The reaction was then quenched by the addition of water (10 mL). The resulting solution was extracted with ethyl acetate (10 mL x 3) and the organic layers combined. The resulting mixture was washed with brine (10 mL x 1). The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. This resulted in 230.0 mg (94%) of 4-[[(1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4- tetramethylcyclobutyl]carbamoyl]phenyl acetate as a light brown solid. LC-MS (ES+): m/z 441.00 [MH+]

Reference： [1]Current Patent Assignee: ARVINAS - WO2017/11590, 2017, A1 Location in patent: Paragraph 00365; 00366

52
[ 2345-34-8 ]
4-((1R,3R)-3-amino-2,2,4,4-tetramethylcyclobutoxy)-2-chlorobenzonitrile hydrogen chloride [ No CAS ]
4-[[(1,3-trans)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl]carbamoyl]phenyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	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 20℃; for 2h;	5.3 Synthesis of 4-[[(1,3-trans)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl]carbamoyl]phenyl acetate Into a 25-mL round-bottom flask, was placed a solution of 4-(acetyloxy)benzoic acid (100.0 mg, 0.56 mmol, 1.00 equiv) in N,N-dimethylformamide (10 mL), 2-chloro-4-[(1,3-trans)-3-amino-2,2,4,4-tetramethylcyclobutoxy]benzonitrile (190.0 mg, 0.68 mmol, 1.10 equiv), HATU (253.0 g, 665.39 mmol, 1.20 equiv), DIEA (0.5 mL, 5.00 equiv). The resulting solution was stirred for 2 h at room temperature. The reaction was then quenched by the addition of water (10 mL). The resulting solution was extracted with ethyl acetate (10 mL3) and the organic layers were combined. The resulting mixture was washed with brine (10 mL1). The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. This resulted in 230.0 mg (94%) of 4-[[(1,3-trans)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl]carbamoyl]phenyl acetate as a light brown solid. LC-MS (ES+): m/z 441.00 [M+H+], tR=1.09 min

Reference： [1]Current Patent Assignee: ARVINAS - US2017/8904, 2017, A1 Location in patent: Paragraph 0395; 0398

53
[ 2345-34-8 ]
[ 2150-46-1 ]
C₂₆H₂₀O₁₀ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42.9 g		42.9 g of 4-acetoxybenzoic acid and 0.2 g of pyridine were added to 430 mL of toluene and stirring was performed under a nitrogen atmosphere at 60 C. 34.0 g of thionyl chloride was added dropwise thereto. After dropwise addition, stirring was performed at 60 C. for 4 hours. Toluene was distilled off under a reduced pressure. The obtained residue was added to 230 mL of toluene and stirred while cooling under a nitrogen atmosphere. A 200 mL toluene solution in which 20.0 g of methyl 2,5-dihydroxybenzoate and 33.7 g of triethylamine were dissolved was added dropwise thereto. After dropwise addition, stirring was performed for 4 hours at room temperature. Water was added to the stirred solution and an organic layer was extracted. Next, the organic layer was washed with water and dried with anhydrous magnesium sulfate. Toluene was distilled off under a reduced pressure, and the residue was purified through column chromatography and recrystallization was performed with a mixture (v/v=1/4) of ethyl acetate and heptane to obtain 42.9 g of a compound (ex-1). Here, the packing of the chromatography column was silica gel. Here, the eluent was a mixture (v/v=9/1) of toluene and ethyl acetate.

Reference： [1]Patent: US2018/119014,2018,A1 .Location in patent: Paragraph 0276-0277

54
[ 2345-34-8 ]
(±)-N¹-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N²,N²-dimethylethane-1,2-diamine tris(2,2,2-trifluoroacetate) [ No CAS ]
(±)-4-(((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl) (2-(dimethylamino)ethyl)carbamoyl)phenyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%	Stage #1: 4-acetyloxy-benzoic acid With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; triethylamine In dichloromethane at 0℃; for 0.5h; Stage #2: (±)-N¹-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N²,N²-dimethylethane-1,2-diamine tris(2,2,2-trifluoroacetate) In dichloromethane at 20℃; for 24h;	3 4.3 General procedure B: TBTU coupling General procedure: To the solution of the suitable acetylated acid (e.g., 3-acetoxybenzoic acid, 4-acetoxybenzoic acid, 2,4-diacetoxybenzoic acid) or 4-acetoxycinnamic acid (1.0 eq.) in CH2Cl2 (30 mL) at 0 °C, TBTU (1.1 eq.) and Et3N (5.0 eq.) were added, and stirred at 0 °C for 30 min. To the resulting mixture 5 (1.1 eq.) was added, and the mixture was stirred at room temperature for 24 h. The reaction mixture was then transferred into a separating funnel. The organic phase was washed with saturated aqueous NaHCO3 solution (30 mL) and saturated brine solution (30 mL), dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure. The residue was purified by column chromatography using CH2Cl2/MeOH (v/v, 9/1) as eluent. The fractions containing the product were combined to obtain the compounds, which were immediately used in the next step.

Reference： [1]Knez, Damijan; Coquelle, Nicolas; Pišlar, Anja; Žakelj, Simon; Jukič, Marko; Sova, Matej; Mravljak, Janez; Nachon, Florian; Brazzolotto, Xavier; Kos, Janko; Colletier, Jacques-Philippe; Gobec, Stanislav [European Journal of Medicinal Chemistry, 2018, vol. 156, p. 598 - 617]

55
[ 2345-34-8 ]
O-benzylhydroxylamine hydrochloride [ No CAS ]
4-((benzyloxy)carbamoyl)phenyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With 1,2-dichloro-ethane; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 4h; Inert atmosphere;	4-((Benzyloxy)carbamoyl)phenyl acetate (3c) A mixture of compound 2c (0.2 g, 1.11 mmol), o-benzylhydroxylaminehydrochloride (0.19 g, 1.22 mmol), DIPEA(0.39 mL) in DCM (25 mL) was stirred with EDC (0.43 g,2.22 mmol) at room temperature for 4 h. The mixture wasdiluted in DCM (100 mL). The organic layer was washedwith 1 N HCl (100 mL) twice and then with brine(100 mL), dried over Na2SO4, concentrated under reducedpressure to afford compound 3c in 60% yield. 1H NMR(500 MHz, (CDCl3) δ 7.69 (d, J = 8.6 Hz, 2H), 7.41-7.40(m, 2H), 7.37-7.33 (m, 3H), 7.08 (d, J = 8.6 Hz, 2H), 4.98(s, 2H), 2.29 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 169.1,165.7, 153.5, 135.3, 129.6, 129.4, 128.9, 128.7, 128.4,122.0, 121.6, 78.4, 21.2. ESI MS (m/e) = 286.11[M + 1]+.

Reference： [1]Lim, Jiah; Song, Yoojin; Jang, Jung-Hee; Jeong, Chul-Ho; Lee, Sooyeun; Park, Byoungduck; Seo, Young Ho [Archives of Pharmacal Research, 2018, vol. 41, # 10, p. 967 - 976]

56
[ 2345-34-8 ]
[ 65372-54-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: hydrogenchloride / AlCl₃ / (2S)-N-methyl-1-phenylpropan-2-amine hydrate; 1,2,4-Trichlorobenzene 2: hydrogenchloride / water; acetone; acetonitrile

Reference： [1]Current Patent Assignee: ACKER - US6191164, 2001, B1

57
[ 2345-34-8 ]
[ 73183-34-3 ]
[ 480424-70-2 ]

Reference： [1]Angewandte Chemie - International Edition,2018,vol. 57,p. 16721 - 16726
Angew. Chem.,2018,vol. 130,p. 16963 - 16968,6

58
[ 2345-34-8 ]
[ 190067-59-5 ]

Yield	Reaction Conditions	Operation in experiment
83.4%	With sodium periodate; sulfuric acid; iodine; acetic anhydride; acetic acid at 0 - 45℃;	1a-2.1 Step 1: Preparation of Compound 7 Stir at room temperature,Sodium periodate (2.8 g, 12.9 mmol, 0.56 eq) and iodine (2.2 g, 8.7 mmol, 0.37 eq) were sequentially added to a mixed solution of Ac2O (9 mL) and acetic acid (18 mL).After the addition, the ice salt bath was cooled to 0 °C.Concentrated sulfuric acid (17.7 g, 180.4 mmol, 7.8 eq) was added dropwise to the mixture.The internal temperature is controlled not higher than 5 °C. After the dropwise addition, stir for 10 minutes.Compound 6 (4.5 g, 23.2 mmol, 1.0 eq) was then added in portions and added over 30 minutes.The internal temperature is controlled to be no higher than 0 °C.After the addition is completed, it is stirred at room temperature for 1 hour.The temperature was then raised to 30 to 45 ° C and stirred overnight.After HPLC showed the disappearance of the starting material, the ice water bath was cooled to 5 °C.The reaction was quenched by dropwise addition of ice water (20 mL). The internal temperature is controlled to be no higher than 30 °C.Then 15% aqueous Na2SO3 (20 mL) was added.Stir at room temperature for 30 minutes and filter by suction.The filter cake was rinsed with water (20 mL x 2).The resulting solid was dried under vacuum at 40 ° C overnight to yield 6.2 g of white solid.The yield was 83.4%.

Reference： [1]Current Patent Assignee: ZHENJIANG SHENGAN PHARMACEUTICAL CO LTD - CN108640958, 2018, A Location in patent: Paragraph 0087; 0089; 0090; 0091

59
[ 2345-34-8 ]
6-allylamino-3-hydroxy-2-naphthaldehyde [ No CAS ]
4-(8-(allylamino)-2-oxo-2H-benzo[g]chromene-3-yl)phenyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; triethylamine In dichloromethane at 25℃; for 8h;	13 Example 13. Synthesis of Compound 2a; 4-(8-(allylamino)-2-oxo-2H-benzo[g]chromene-3-yl)phenyl acetate A general synthesis pathway of Compound 2a is shown in Reaction Scheme 13 below. The inventors synthesized Compound 2a, that is, 4-(8-(allylamino)-2-oxo-2H-benzo[g]chromene-3-yl)phenyl acetate. Specifically, a known synthesis starting material, that is, Compound e (100 mg, 0.41 mmol) was mixed with 4-acetoxybenzoic acid (120 mg, 0.62 mmol), triethylamine (289 μL, 2.07 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC; 96.5 mg, 0.62 mmol), and 1-hydroxybenzotriazole hydrate (HOBt; 95.2 mg, 0.62 mmol). The resulting mixture was stirred at room temperature for 8 hours and concentrated under reduced pressure, and a crude product was purified by column chromatography in which it was passed through silica gel (eluent: MeOH/CH2Cl2=3/97), thereby obtaining an orange solid, Compound 2a (126 mg, 80%). 1H NMR (CDCl3, 300 MHz, 296 K): δ 7.84 (d, 2H, J=5.7 Hz), 7.74 (d, 2H, J=6.6 Hz), 7.69 (d, 1H, J=9.0 Hz), 7.45 (s, 1H), 7.19 (s, 1H), 7.16 (s, 1H), 6.89 (d, 1H, J=9.0 Hz), 6.77 (d, 1H, J=2.1 Hz), 6.02 (m, 1H, J=38 Hz), 7.35 (d, 1H, J=17 Hz), 5.25 (d, 1H, J=11 Hz), 4.27 (t, 1H, J=11 Hz), 3.94 (d, 2H, J=3.6 Hz), 2.33 (s, 3H).

Reference： [1]Current Patent Assignee: POHANG UNIVERSITY OF SCIENCE AND TECHNOLOGY - US2018/371256, 2018, A1 Location in patent: Paragraph 0142-0145

60
[ 2345-34-8 ]
[ 112940-58-6 ]
[4-[[4-[4-(2-pyridyl)piperazin-1-yl]phenyl]carbamoyl]phenyl] acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	Stage #1: 4-acetyloxy-benzoic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 1.5h; Stage #2: 4-[4-(pyridin-2-yl)piperazin-1-yl]phenylamine With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 1.25h;	137.a a) 4-((4-(4-(Pyridin-2-yl)piperazin-l-yl)phenyl)carbamoyl)phenyl acetate 4-Acetoxybenzoic acid (1.5 g, 8.33 mmol) was dissolved in DCM (60 ml). Oxalyl chlo ride (1.58 g, 1.09 ml, 12.5 mmol) was added followed by DMF (30.4 mg, 32.2 m, 416 miho). The reaction mixture was stirred for 1.5 h at rt, then concentrated under vacuum. The crude product was dissolved in DCM (35 ml) and added dropwise to a stirred solution of 4-(4-(pyri- din-2-yl)piperazin-l-yl)aniline (Intermediate l.b) (2.12 g, 8.33 mmol) and DIPEA (4.31 g, 5.82 ml, 33.3 mmol) in DCM (70 ml) at RT. The reaction mixture was stirred at rt for 1.25 h. To the light brown suspension was added a mixture of MeOH (6 ml) and H20 (30 ml) and the reaction mixture was allowed to stir for 15 minutes before filtering off the product. The filter cake was washed with DCM (20 ml) and H20 (2 x 30 ml). Colorless solid (2.89 g, 83%), LC- MS: m/z = 417.3 [M+H]+

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2019/121661, 2019, A1 Location in patent: Page/Page column 98

61
[ 2345-34-8 ]
6-[4-(4-aminophenyl)piperazin-1-yl]pyridine-3-carbonitrile [ No CAS ]
[4-[[4-[4-(5-cyano-2-pyridyl)piperazin-1-yl]phenyl]carbamoyl]phenyl] acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	Stage #1: 4-acetyloxy-benzoic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20 - 25℃; for 1.5h; Stage #2: 6-[4-(4-aminophenyl)piperazin-1-yl]pyridine-3-carbonitrile With N-ethyl-N,N-diisopropylamine In dichloromethane at 20 - 25℃; for 0.5h;	108.a a) [4-[[4-[4-(5-Cyano-2-pyridyl)piperazin-l-yl]phenyl] carbamoyl]phenyl] acetate To a solution of 4-acetoxybenzoic acid (1.29 g, 7.16 mmol) in DCM (60 ml) were added oxalyl chloride (1.36 g, 940 m, 10.7 mmol) and DMF (26.2 mg, 27.7 m, 358 miho) and the mixture stirred at 20-25°C for 1.5 h. The reaction mixture was concentrated under vacuum. The crude product was dissolved in DCM (30 ml) and added to a solution of 6-[4- (4-aminophenyl)piperazin-l-yl]pyridine-3-carbonitrile (Intermediate 50. a) (2.0 g, 7.16 mmol) and DIPEA (3.7 g, 5.0 ml, 28.6 mmol) in DCM (60 ml). The light brown suspension was stirred at 20-25°C for 30min. Then MeOH (6 ml) was added to quench the reaction. The sus pension was stirred for 1 h and filtered. The cake was washed with DCM (10 ml) and dried on the filter for 2 min. Then the cake was washed with H20 (25 ml) and finally dried under vacuum at 40 °C to obtain the desired product (2.91 g, 92%) as colorless crystals. LC MS m/z = 442.3 [M+H]+.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2019/121661, 2019, A1 Location in patent: Page/Page column 77; 78

62
[ 2345-34-8 ]
[ 2687-43-6 ]
4-((benzyloxy)carbamoyl)phenyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 4h;	5 5. 4-((benzyloxy) carbamoyl) phenyl acetate [4-((benzyloxy) carbamoyl) phenyl acetate; 3c] Compound 2c (0.2 g, 1.11 mmol),o-benzylhydroxylamine hydrochloride (0.19 g, 1.22 mmol),DCM (25 mL) mixture with DIPEA (0.39 mL) was stirred with EDC (0.43 g, 2.22 mmol) at room temperature for 4 hours.The mixture was diluted with DCM (100 mL). The organic layer was washed twice with 1N HCl (100 mL), brine (100 mL), dried over Na 2 SO 4, concentrated under reduced pressure to give compound 3c in 60% yield.

Reference： [1]Current Patent Assignee: KEIMYUNG UNIVERSITY - KR102023845, 2019, B1 Location in patent: Paragraph 0086-0089; 0154; 0155

63
[ 2345-34-8 ]
[ 98-80-6 ]
[ 24262-65-5 ]

Yield	Reaction Conditions	Operation in experiment
81%	With pyridine; di-tert-butyl peroxide; C₁₂₂H₁₀₄Cu₄Na₄O₂₈P₄Si₁₂ In acetonitrile at 130℃; for 0.666667h; Sealed tube; Microwave irradiation;	General procedure General procedure: 0.3 mmol of corresponding aromatic carboxylicacid, 0.45 mmol of corresponding aromatic boronic acid,catalyst Cu-3 (11 μmol, 32 mg), 0.3 mmol of Py and 0.45 mmol of(tBuO)2 were dissolved in 3 mL of MeCN. The reaction was carriedout 20 min at 130 °C in sealed vial inMWconditions. After the firststep were added the new portion of 0.45 mmol of correspondingaromatic boronic acid and 0.45 mmol of (tBuO)2 in the vial, andreaction was conducted at the same conditions as in a first step(sealed vial, 130 °C, 20 min). Solvent was then evaporated undervacuum and the obtained residue was purified by flash chromatographyon silica gel to give corresponding carboxylic ester (3a-g).

Reference： [1]Astakhov, G. S.; Bantreil, X.; Bilyachenko, A. N.; Dorovatovskii, P. V.; Khrustalev, V. N.; Lamaty, F.; Levitsky, M. M.; Shubina, E. S.; Zubavichus, Y. V. [Journal of Organometallic Chemistry, 2020, vol. 906]

64
[ 2345-34-8 ]
C₁₅H₂₉N₃O₅ [ No CAS ]
4-(2,3-bis(tert-butoxycarbonyl)guanidino)butyl 4-acetoxybenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;	4.1.6. Procedure for the synthesis of compounds 13a-13t General procedure: The mixture of 6c (1 equiv, 0.83 mmol), various acids (1 equiv,0.83 mmol), EDCI (1.2 equiv, 1.0 mmol), and DMAP (catalyticamount) were stirred in DCM (20 mL) at room temperature for2e18 h. 20 mL DCM was added after the completion of the reaction,the organic layer was washed with water (20 mL) and brine(20 mL), dried over Na2SO4, and concentrated to afford crudeproducts which were purified by flash chromatography (DCM/MeOH, 40:1) to provide 13a-13t as white solids (83e98%).

Reference： [1]Liu, Junkai; Luo, Shanshan; Ma, Fenfen; Xu, Shengtao; Zhu, Yi Zhun [European Journal of Medicinal Chemistry, 2020, vol. 200]

65
[ 2345-34-8 ]
[ 21209-51-8 ]
3-(benzyloxy)-2-(((benzyloxy)carbonyl)amino)-3-oxopropyl 4-acetoxybenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73.3%	With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 4.08h; Inert atmosphere; Cooling with ice;	5.1.1. Preparation of 3-(benzyloxy)-2-(((benzyloxy)carbonyl)amino)-3-oxopropyl 4-acetoxybenzoate (MK4) MK4 was synthesized starting from the commerciallyavailable N-benzyloxycarbonyl-L-serine benzyl ester and 4-acetoxybenzoic acid. The ester (1 mol eq, 548.43 mg, 1.665mmol) along with the acid (1 mol eq, 300 mg, 1.665 mmol)and dimethylaminepyridine (DMAP) (0.3 mol eq, 61.5 mg,0.5 mmol) were dissolved in dry dichloromethane (2 mL) ina round-bottomed flask under nitrogen and kept in an icebath. N,N’-dicyclohexylcarbodiimide (DCC) (1 mol eq,343.58 mg, 1.665 mmol) was dissolved in 6 mL of dry dichloromethane and added in the flask. After the addition, thereaction was left to stir for 5 min in ice and for 4 h at roomtemperature under nitrogen. The mixture was then filtered to remove the formed dicyclohexylurea (DCU) and the filtratewas concentrated in vacuo. The crude was redissolved in drydichloromethane, and a new filtration was performed to removeany residual DCU. The filtrate was washed twice with1 M HCl and once with 0.1 M NaOH and the organic layer was dried over sodium sulphate for more than 2 h. After thefiltration of the sodium sulphate, the solvent was removed invacuo and the crude was dissolved in isopropanol with gentleheating. The solution was left in the freezer for the finalproduct to crystallize as a white waxy solid (600 mg, 73.3%yield).1H NMR (MeOD, TMS, ppm) δ 7.93 - 7.92 (d, J= 7Hz,2H, Ar-H3, H5), 7.34 - 7.23 (m, 11H, NH, Ar-H2’, H3’,H4’, H5’, H6’, H2’’, H3’’, H4’’, H5’’, H6’’) 7.16 - 7.15 (d,J= 7Hz, 2H, Ar-H2, H6), 5.26 - 5.11 (m, 4H, COOCH2Ph,NHCOOCH2Ph), 4.75 - 4.56 (m, 3H, CH2-CH), 2.34 - 2.30(m, 3H, CH3). 13C NMR (CDCl3, TMS, ppm) δ 169.33(C=O, CH3COO), 168.77 (C=O, COOCH2Ph), 165.09 (C=O,Ar-COO-CH2-CH), 155.70 (C=O, NH-COO-CH2Ph), 154.59(Ar-C1), 135.97 (Ar-C1’’), 134.84 (Ar-C1’), 131.92 (2C, Ar-C3, C5), 131.39 (2C, Ar-C3’, C5’), 131.30 (2C, Ar-C3’’,C5’’), 128.64 (2C, Ar-C4’, C4’’), 128.58 (Ar-C2’), 128.46(Ar-C6’), 128.31 (Ar-C2’’), 128.19 (Ar-C6’’), 126.73 (Ar-C4), 122.01 (Ar-C2), 121.71 (Ar-C6), 67.86 (NH-COOCH2Ph),67.32 (CH-COO-CH2Ph), 64.86 (Ar-COO-CH2-CH), 53.59 (CH), 21.17 (CH3). HRMS-ESI m/z Calculatedfor C27H26NO8 [M+H+] 492.1658, found 492.1970.

Reference： [1]Kourti, Malamati; Cai, Jun; Jiang, Wen; Westwell, Andrew D. [Medicinal Chemistry, 2021, vol. 17, # 1, p. 40 - 59]

66
[ 24262-66-6 ]
[ 2345-34-8 ]

Yield	Reaction Conditions	Operation in experiment
99%	With iodine; aluminium In acetonitrile at 80℃; for 18h;
99%	With iodine; aluminium In acetonitrile at 80℃; for 18h;	1; 2 Example 1 (methyl 4-acetoxybenzoate demethylated) To a 100ml round bottom flask was added 4-acetoxy methyl benzoate (0.971g, 5mmol), iodine (0.951g, 3.75mmol), excess aluminum powder and acetonitrile (40ml), stirred at 80 ° C for 18 hours, after the reaction was completed with 2M dilute hydrochloric acid (5ml) quenched, and then extracted with ethyl acetate (50ml) three times, combined organic phase, first washed with sodium thiosulfate saturated aqueous solution (10ml), and then dried with anhydrous magnesium sulfate, filtered, The filtrate was removed by a rotary evaporator to give 0.892g of 4-acetoxybenzoic acid (white solid, yield 99%).

Reference： [1]Sang, Dayong; Yue, Huaxin; Fu, Yang; Tian, Juan [Journal of Organic Chemistry, 2021, vol. 86, # 5, p. 4254 - 4261]
[2]Current Patent Assignee: UNIV JINGCHU TECHNOLOGY - CN114573453, 2022, A Location in patent: Paragraph 0021-0028

67
[ 2345-34-8 ]
[ 95-53-4 ]
[ 54393-58-7 ]

Yield	Reaction Conditions	Operation in experiment
82.7%	Stage #1: 4-acetyloxy-benzoic acid With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 2h; Cooling with ice; Stage #2: <i>o</i>-toluidine With triethylamine In dichloromethane at 20℃; for 5h; Cooling with ice;	27 Synthesis of 4-(2-Methylphenylcarbamoyl) Phenyl Acetate (27C) Compound 27B (1g, 5.15mmol)Dissolve in 5mL anhydrous dichloromethane,Slowly add oxalyl chloride (1.96g, 15.45mmol) in an ice bath,Add 2 drops of DMF,Remove the ice bath,Reaction at room temperature for 2h,Remove the solvent and excess oxalyl chloride under reduced pressure,Add 3mL of anhydrous dichloromethane to dissolve,Slowly drip it into 2-methylaniline (549.31mg, 5.13mmol) in an ice bathAnd triethylamine (2.07g, 20.51mmol)Mixed dichloromethane (4mL) solution,Remove the ice bath,React at room temperature for 5h.Spin off the solvent,Add 20mL water,Ethyl acetate extraction (3×15mL),Combine the organic phases,Dry with anhydrous sodium sulfate,Filter, concentrate under reduced pressure,Purification by silica gel column chromatography (PE:EA=4:1),1.2 g of white solid was obtained, the yield was 82.7%

Reference： [1]Current Patent Assignee: CHINA PHARMACEUTICAL UNIVERSITY; NANJING ZHONGAO CONVERSION MEDICINE RES INSTITUTE - CN112778154, 2021, A Location in patent: Paragraph 0261; 0262; 0267; 0268

68
[ 2345-34-8 ]
[ 108-98-5 ]
C₁₄H₁₂O₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	With bis(1,5-cyclooctadiene)nickel ⁽⁰⁾; 1,3-bis-(diphenylphosphino)propane In acetonitrile at 140℃; for 12h;	11 Preparation Example 11 Add 0.2 mmol of aryl carboxylic acid (Ar = 4-acetoxyphenyl), 0.24 mmol of thiophenol (R = phenyl) into a 10 mL reaction tube, and add 10mol% bis-(1,5-cyclooctadiene) nickel , 1,3-bis(diphenylphosphine)propane 30 mol%, tert-valeric acid anhydride 150 mol%, acetonitrile as solvent, reaction at 140 °Cfor 12 h. After the reaction, the target compound arylalkynes (Ar=4-acetoxyphenyl, R=phenyl) was separated by column chromatography, and a colorless liquid was obtained with a yield of 62%.

Reference： [1]Current Patent Assignee: HAINAN UNIVERSITY - CN113698327, 2021, A Location in patent: Paragraph 0020

69
[ 1452-63-7 ]
[ 2345-34-8 ]
N-4-acetoxybenzoyl-N’-picolinoylhydrazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	Stage #1: p-Hydroxybenzoic acid acetate With thionyl chloride In chloroform; N,N-dimethyl-formamide at 60℃; for 16h; Inert atmosphere; Stage #2: picolinic acid hydrazide With triethylamine In chloroform at 60℃; for 16h;	N-4-acetoxybenzoyl-N’-picolinoylhydrazine (IIb) and N-4-methoxycarbonylbenzoyl-N’-picolinoylhydrazine (IIIa). A suspensionof Ib (5.0 g, 27.7 mmol) in 20 mL of CHCl3, 6 mL of SOCl2 and threedrops of DMF under nitrogen atmosphere dissolved rapidly when heatedto 60 C. Evaporation of the solution after 16 h of stirring under nitrogenyielded a white solid which was re-dissolved in 20 mL of CHCl3 and solidpicolinic hydrazide (3.8 g, 27.7 mmol) was added. A voluminous precipitatethat formed disappeared with dropwise addition of TEA (3.1 g,30.5 mmol) and the clear solution was heated to 60 C for 16 h. The solidproduct, which was obtained after evaporating CHCl3 was treated with100 mL of water and stirred for 4 h, and then was filtrated and washedseveral times with water. Recrystallization of the crude white powder inethyl acetate:acetone (1:1, v/v) yielded colourless elongated crystals ofIIb.The reaction yielding IIIa was performed analogically, using IIa (3.2g, 17.7 mmol) as a starting material. Recrystallization from toluene:MeOH (1:1, v/v) yielded colourless crystals of IIIa.
86%	Stage #1: p-Hydroxybenzoic acid acetate With thionyl chloride; N,N-dimethyl-formamide In chloroform at 60℃; for 16h; Inert atmosphere; Stage #2: picolinic acid hydrazide With triethylamine In chloroform at 60℃; for 16h;	N-4-acetoxybenzoyl-N’-picolinoylhydrazine (IIb) and N-4-methoxycarbonylbenzoyl-N’-picolinoylhydrazine (IIIa). A suspensionof Ib (5.0 g, 27.7 mmol) in 20 mL of CHCl3, 6 mL of SOCl2 and threedrops of DMF under nitrogen atmosphere dissolved rapidly when heatedto 60 C. Evaporation of the solution after 16 h of stirring under nitrogenyielded a white solid which was re-dissolved in 20 mL of CHCl3 and solidpicolinic hydrazide (3.8 g, 27.7 mmol) was added. A voluminous precipitatethat formed disappeared with dropwise addition of TEA (3.1 g,30.5 mmol) and the clear solution was heated to 60 C for 16 h. The solidproduct, which was obtained after evaporating CHCl3 was treated with100 mL of water and stirred for 4 h, and then was filtrated and washedseveral times with water. Recrystallization of the crude white powder inethyl acetate:acetone (1:1, v/v) yielded colourless elongated crystals ofIIb.The reaction yielding IIIa was performed analogically, using IIa (3.2g, 17.7 mmol) as a starting material. Recrystallization from toluene:MeOH (1:1, v/v) yielded colourless crystals of IIIa. Colourless crystals. Yield 86 %. EA (calc.) for C15H13N3O4(299.29): C, 60.20; H, 4.38; N, 14.04 %; found: C, 59.64; H, 4.53; N,13.76 %. 1H NMR (400 MHz, DMSO-d6, 298 K, ppm): δ 10.65 (s, 1H),10.58 (s, 1H), 8.71 (d, J = 4.7 Hz, 1H), 8.08-8.02 (m, 2H), 7.97 (d, J =8.5 Hz, 2H), 7.66 (d, J = 6.8 Hz, 1H), 7.29 (d, J = 8.5 Hz, 2H), 2.31 (s,3H).

Reference： [1]Štarha, Pavel; Koczurkiewicz-Adamczyk, Paulina; Masaryk, Lukáš; Milde, David; Słoczyńska, Karolina; Zahradniková, Eva; Zoufalý, Pavel [Inorganica Chimica Acta, 2022, vol. 536]
[2]Štarha, Pavel; Koczurkiewicz-Adamczyk, Paulina; Masaryk, Lukáš; Milde, David; Słoczyńska, Karolina; Zahradniková, Eva; Zoufalý, Pavel [Inorganica Chimica Acta, 2022, vol. 536]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	2345-34-8	MDL No. :	MFCD00002540
Formula :	C₉H₈O₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	GDBUZIKSJGRBJP-UHFFFAOYSA-N
M.W :	180.16	Pubchem ID :	16865
Synonyms :

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.11
Num. rotatable bonds :	3
Num. H-bond acceptors :	4.0
Num. H-bond donors :	1.0
Molar Refractivity :	44.9
TPSA :	63.6 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) :	-6.35 cm/s

Log Po/w (iLOGP) :	1.49
Log Po/w (XLOGP3) :	1.48
Log Po/w (WLOGP) :	1.31
Log Po/w (MLOGP) :	1.51
Log Po/w (SILICOS-IT) :	1.1
Consensus Log Po/w :	1.38

[ CAS No. 2345-34-8 ]

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[ 2345-34-8 ] Synthesis Path-Downstream 1~69

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[ 2345-34-8 ]

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Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.56

Log S (ESOL) :	-2.03
Solubility :	1.67 mg/ml ; 0.00927 mol/l
Class :	Soluble
Log S (Ali) :	-2.42
Solubility :	0.681 mg/ml ; 0.00378 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-1.85
Solubility :	2.57 mg/ml ; 0.0143 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.26

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

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[ CAS No. 2345-34-8 ]

Quality Control of [ 2345-34-8 ]

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