Name: 27914-73-4|4-(Chlorocarbonyl)phenyl acetate|95%
Brand: Ambeed
SKU: A591578
Rating: 93 (22 reviews)

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]
[86]Kubica, Krzysztof P.; Taciak, Przemysław P.; Czajkowska, Agnieszka; Stokfisz-Ignasiak, Alicja; Wyrebiak, Rafał; Podsadni, Piotr; Młynarczuk-Biały, Izabela; Malejczyk, Jacek; Mazurek, Aleksander P. [Acta poloniae pharmaceutica, 2018, vol. 75, # 4, p. 891 - 901]
[87]Current Patent Assignee: ROCHE HOLDING AG - US4177280, 1979, A
[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]
[89]Hu, Jiantao; Hu, Biao; Wang, Mingliang; Xu, Fuming; Miao, Bukeyan; Yang, Chao-Yie; Wang, Mi; Liu, Zhaomin; Hayes, Daniel F.; Chinnaswamy, Krishnapriya; Delproposto, James; Stuckey, Jeanne; Wang, Shaomeng [Journal of Medicinal Chemistry, 2019, vol. 62, # 3, p. 1420 - 1442]
[90]Spasov; Brel; Litvinov; Lisina; Kucheryavenko; Budaeva, Yu. N.; Salaznikova; Rashchenko; Shamshina; Batrakov; Ivanov [Russian Journal of Bioorganic Chemistry, 2018, vol. 44, # 6, p. 769 - 777][Bioorg. Khim., 2018, vol. 44, # 6, p. 769 - 777,9]
[91]Current Patent Assignee: UENO FINE CHEMICALS INDUSTRY,LTD. - JP2019/26590, 2019, A Location in patent: Paragraph 0062
[92]Sosonyuk, Sergey E.; Peshich, Anita; Tutushkina, Anastasia V.; Khlevin, Dmitry A.; Lozinskaya, Natalia A.; Gracheva, Yulia A.; Glazunova, Valeria A.; Osolodkin, Dmitry I.; Semenova, Marina N.; Semenov, Victor V.; Palyulin, Vladimir A.; Proskurnina, Marina V.; Shtil, Alexander A.; Zefirov, Nikolay S. [Organic and Biomolecular Chemistry, 2019, vol. 17, # 10, p. 2792 - 2797]
[93]Current Patent Assignee: ROCHE HOLDING AG - WO2019/121661, 2019, A1 Location in patent: Page/Page column 23; 24
[94]Current Patent Assignee: TRANSFUSION HEALTH LLC - WO2019/84452, 2019, A1 Location in patent: Paragraph 0432
[95]Bi, Jingjie; Wang, Wenqing; Du, Junxi; Chen, Kun; Cheng, Kui [European Journal of Medicinal Chemistry, 2019, vol. 179, p. 233 - 245]
[96]Zhao, Peng-Fei; Liu, An; Wei, Ming-Guang; Liu, Zai-Qun [Journal of Organic Chemistry, 2019, vol. 84, # 24, p. 15854 - 15864]
[97]Brel’; Spasov; Lisina; Popov; Kucheryavenko; Litvinov; Salaznikova; Rashchenko [Pharmaceutical Chemistry Journal, 2019, vol. 53, # 6, p. 511 - 515]
[98]Bo, Yong-Xin; Chen, Shi-Wu; Hao, Shu-Yi; Wang, Xing-Rong; Xiang, Rong; Xu, Yu [Bioorganic and medicinal chemistry, 2020, vol. 28, # 5]
[99]Chen, Cheng; Gao, Han; Liu, Ya; Sun, Le-Yun; Yang, Ke-Wu; Zhen, Jian-Bin [2020, vol. 11, # 2, p. 259 - 267]
[100]Current Patent Assignee: UNIVERSITY OF MICHIGAN - WO2020/142227, 2020, A1 Location in patent: Paragraph 0181-0182

2
[ 27914-73-4 ]
[ 75-75-2 ]
[ 82957-06-0 ]
[ 82955-84-8 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1985,vol. 33,p. 1458 - 1471

3
[ 27914-73-4 ]
[ 20059-73-8 ]
Acetic acid 4-[4-(2-dimethylamino-ethoxy)-benzylcarbamoyl]-phenyl ester [ No CAS ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1992,vol. 40,p. 202 - 211

4
[ 27914-73-4 ]
[ 123-31-9 ]
[ 79066-38-9 ]

Yield	Reaction Conditions	Operation in experiment
90%	With pyridine In 1,2-dichloro-ethane at 20℃; for 48h; Inert atmosphere;	Bis(4-acetoxybenzoyloxy)-1,4-benzene Into a 500 mL three necked round bottom flask,equipped with magnetic stirrer, nitrogen inlet andcalcium chloride guard tube, hydroquinone (4.4 g,0.04 mol) and pyridine (25 mL, 0.3 mol) were placedand the mass stirred till dissolution. 4-Acetoxybenzoyl chloride (23.82 g, 0.12 mol) in dry1,2-dichloroethane (300 mL) was taken in anotherflask and this solution was added to the hydroquinonesolution. The reaction mixture was stirred undernitrogen blanket for 48 hr at RT and the mixture waswashed successively with 5% sodium carbonatesolution, 5% hydrochloric acid and distilled water.Dichloroethane layer was concentrated to dryness ona rotary evaporator. The crude product was purifiedby recrystallization from chloroform/petroleum ether(60-80°C) solvent mixture. The solution was filtered and the obtained solid mass was dried under reducedpressure at 80°C for 4 hr. Yield: 90%; m.p. 186-87°C;IR (Nujol): 1723 cm-1 (C=0 stretching); 1H NMR(CDCl3): d 2.2 (s, 6H), 7.1 (d, 8H) and 8.1 (d, 4H).

Reference： [1]Mulani, Khudbudin B.; Ganjave, Nitin V.; Chavan, Nayaku N. [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2014, vol. 53, # 5, p. 591 - 596]
[2]Hempel, Erika; Lindau, Juergen; Roetz, Uwe; Fischer, Hartmut; Utschick, Hermann; Kuschel, Frank [Molecular Crystals and Liquid Crystals (1969-1991), 1990, vol. 193, p. 199 - 204]

5
[ 27914-73-4 ]
[ 21867-64-1 ]
Acetic acid 4-(4-propyl-piperazine-1-carbonyl)-phenyl ester; hydrochloride [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,1996,vol. 31,p. 669 - 673

6
[ 27914-73-4 ]
[ 99-59-2 ]
[ 180136-46-3 ]

Yield	Reaction Conditions	Operation in experiment
82%	With triethylamine In dichloromethane for 20h; Ambient temperature;

Reference： [1]Ashton, Michael J.; Brown, Thomas J.; Fenton, Garry; Halley, Frank; Harper, Mark F.; Lockey, Peter M.; Porter, Barry; Roach, Alan G.; Stuttle, Keith A. J.; Vicker, Nigel; Walsh, Roger J. A. [Journal of Medicinal Chemistry, 1996, vol. 39, # 17, p. 3343 - 3356]

7
[ 27914-73-4 ]
sodium compound of α,γ-dimethoxy-acetoacetic acid ethyl ester [ No CAS ]
[ 32136-81-5 ]

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

8
[ 27914-73-4 ]
[ 56414-96-1 ]
4-hydroxy-<i>N</i>-(2-morpholin-4-yl-2-oxo-ethyl)-benzamide [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,1999,vol. 34,p. 1023 - 1034

9
[ 27914-73-4 ]
[ 137686-07-8 ]
[ 607358-20-3 ]

Reference： [1]Organic Letters,2003,vol. 5,p. 3233 - 3236

10
[ 27914-73-4 ]
[ 359586-15-5 ]
[ 359586-16-6 ]

Yield	Reaction Conditions	Operation in experiment
51%	With sodium hydroxide; tetrabutyl-ammonium chloride In dichloromethane at 20℃; for 0.5h;
	With sodium hydroxide; tetrabutyl-ammonium chloride In dichloromethane
	With sodium hydroxide; tetrabutyl-ammonium chloride In dichloromethane at 20℃; for 1h;	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 sodium hydroxide; tetrabutyl-ammonium chloride In dichloromethane

R.26 1-(4-Acetoxybenzoyl)-2-methylindole-4-acetic Acid Benzyl Ester To a solution of the compound (400 mg) prepared in Reference Example 25 in methylene chloride (7 ml) was added sodium hydroxide (286 mg) and tetrabutylammonium chloride (20 mg) at room temperature. The mixture was added the above-mentioned solution of 4-acetoxybenzoyl chloride in methylene chloride (3 ml), and the mixture was stirred at room temperature overnight. The reaction mixture was filtrated, and the filtrate was concentrated. The residue was purified by column chromatography on silica gel (n-hexane:ethyl acetate=7:3) to give the title compound (500 mg) having the following physical data. TLC: Rf 0.34(n-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).

Reference： [1]Torisu, Kazuhiko; Kobayashi, Kaoru; Iwahashi, Maki; Nakai, Yoshihiko; Onoda, Takahiro; Nagase, Toshihiko; Sugimoto, Isamu; Okada, Yutaka; Matsumoto, Ryoji; Nanbu, Fumio; Ohuchida, Shuichi; Nakai, Hisao; Toda, Masaaki [Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 20, p. 5361 - 5378]
[2]Torisu, Kazuhiko; Kobayashi, Kaoru; Iwahashi, Maki; Nakai, Yoshihiko; Onoda, Takahiro; Nagase, Toshihiko; Sugimoto, Isamu; Okada, Yutaka; Matsumoto, Ryoji; Nanbu, Fumio; Ohuchida, Shuichi; Nakai, Hisao; Toda, Masaaki [Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 19, p. 4891 - 4895]
[3]Current Patent Assignee: ONO PHARMACEUTICAL CO LTD - EP1424325, 2004, A1 Location in patent: Page 103
[4]Current Patent Assignee: ONO PHARMACEUTICAL CO LTD - US2003/176400, 2003, A1

11
[ 27914-73-4 ]
1'-[(3S)-3-(3,4-dichlorophenyl)-4-(methylamino)butyl]-N,N-dimethyl-1,4'-bipiperidine-4'-carboxamide trihydrochloride [ No CAS ]
4-([(2S)-2-(3,4-dichlorophenyl)-4-{4'-[(-N,N-dimethylamino)-carbonyl]1,4'-bipiperidin-1'-yl}butyl](methyl)amino}carbonyl)phenyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With triethylamine In dichloromethane at 20℃; for 15h;	14 220 mg (0.00038 mole) of 1'-[(3S)-3-(3,4-dichlorophenyl)-4-(methylamino)butyl]-N,N-dimethyl-1,4'-bipiperidine-4'-carboxamide were dissolved in 20 ml of methylene chloride in the presence of 200 μl of triethylamine under stirring at room temperature. To the reaction mixture, were added drop wise at room temperature, a solution of 98 mg of 4-acetoxybenzoyl chloride in 20 ml of methylene chloride and subsequently 200 μl of triethylamine were added. The reaction mixture was stirred for 15 hours at room temperature and concentrated in vacuum. The residue was dissolved in 50 ml of ethyl acetate and 30 ml of MTBE in the presence of 200 mg potassium hydroxide dissolved in 20 ml of water. The organic phase was separated and washed 4 times with 20 ml of water. The organic layer was recovered, dried on sodium sulfate and concentrated to dryness to deliver 240 mg (quantitative yield) of 4-([(2S)-2-(3,4-dichlorophenyl)-4-{4'-[(dimethylamino)carbonyl]-1,4'-bipiperidin-1'-yl}butyl](methyl)amino}carbonyl)phenyl acetate as a glassy material. LC-MS: M+1 (monoisotope): 631. Retention time: 7.78 min (API). 1HNMR (as base) (500 MHz, CDCl3) δ: 7.45-7.1 (m, 7H), 7.0, 6.8 (2×bs, 0.7H), 3.82 (bs, 0.7H), 3.55 (dd, 1H), 3.5-3.2 (m, 4H), 3.1 (bs, 0.7H), 3.0 (m, 2H), 2.95-2.90 (2×s, 3H), 2.8-2.5 (m, 4.5H), 2.3 (s, 3H) 2.25-1.6 (m, 12H), 1.5 (s, 4H), 1,4 (s, 2H). 13CNMR (125 MHz, CDCl3) δ: 170.7, 168.2, 150.7, 131.7, 121.5, 120.9, 66.1, 55.2, 56.1, 52.6, 51.7, 50.9, 50.4, 46.6, 40.9, 38.0, 36.9, 29.9, 26.2, 24.4, 20.4

Reference： [1]Current Patent Assignee: ABBVIE INC - US2007/219214, 2007, A1 Location in patent: Page/Page column 30

12
[ 99-96-7 ]
[ 27914-73-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 63 percent / aq. NaOH / 1 h / cooling 2: thionyl chloride; N,N-dimethylformamide / 5 h / 70 °C
	With thionyl chloride In acetic anhydride	Synthetic Method C Synthetic Method C Esters of non-volatile or acid-unstable alcohols were prepared in a manner analogous to that described below for compound 25. A suspension of 7.0-7.4 moles 4-hydroxybenzoic acid in 18.8-19.2 moles of acetic anhydride is stirred over a steam bath. On addition of a catalytic amount (0.5-1.5 ml) of concentrated sulfuric acid rapid dissolution of the 4-hydroxybenzoic acid occurred and was followed immediately by precipitation of product. This mixture was warmed by the steam bath an additional 30-60 minutes then cooled to room temperature. The slurry obtained was filtered and the filter cake was washed with water. The white solid obtained in this manner was 4-acetoxybenzoic acid and was used without further purification. A mixture of the above product and thionyl chloride (1:6 ratio) was stirred at reflux for 16-18 hours. All volatiles were then removed under reduced pressure to give 4-acetoxybenzoyl chloride, a beige solid which was used without further purification.
	Multi-step reaction with 2 steps 1: 6 h / Reflux 2: thionyl chloride / 2 h / Reflux

	Multi-step reaction with 2 steps 1: pyridine / 4 h / 20 °C 2: oxalyl dichloride / 4 h / 20 °C
	Multi-step reaction with 2 steps 1.1: sulfuric acid / 1 h 1.2: 3 h 2.1: thionyl chloride / benzene / 2 h / Reflux
	Multi-step reaction with 2 steps 1: pyridine / 12 h / 20 °C 2: thionyl chloride / 3 h / Reflux
	Multi-step reaction with 2 steps 1: sodium hydroxide / water / 4 h / 20 °C 2: thionyl chloride / 8 h / Reflux
	Multi-step reaction with 2 steps 1: pyridine 2: thionyl chloride; N,N-dimethyl-formamide
	Multi-step reaction with 2 steps 1: 4 h / 111.84 °C 2: thionyl chloride / 5 h / 81.84 °C
	Multi-step reaction with 2 steps 1: pyridine / 4 h / 20 °C 2: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 4 h / 20 °C
	Multi-step reaction with 2 steps 1: sulfuric acid / 3 h / 80 °C / Inert atmosphere 2: oxalyl dichloride; N,N-dimethyl-formamide / acetonitrile / 1 h / 20 °C
	Multi-step reaction with 2 steps 1: triethylamine 2: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane
	Multi-step reaction with 2 steps 1: sulfuric acid / 1 h / 20 °C 2: thionyl chloride / 5 h / 80 °C
	Multi-step reaction with 2 steps 1: pyridine / 0 - 20 °C 2: thionyl chloride / dichloromethane / Reflux
	Multi-step reaction with 2 steps 1: sulfuric acid / 3 h / 60 °C / Inert atmosphere 2: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 3 h / 20 °C / Inert atmosphere; Reflux
	Multi-step reaction with 2 steps 1: acetic anhydride / 4 h / 130 °C 2: thionyl chloride / 4 h / 78 °C
	Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / 1 h / 85 °C 2: thionyl chloride / dichloromethane / 2 h / 20 °C
	Multi-step reaction with 2 steps 1: sodium hydroxide / water / 0 - 20 °C 2: thionyl chloride; pyridine / dichloromethane / Reflux
	Multi-step reaction with 2 steps 1: triethylamine / 6 h / 100 °C 2: oxalyl dichloride / dichloromethane / 6 h / 20 °C
	Multi-step reaction with 2 steps 1: phosphoric acid 2: pyridine; thionyl chloride / 75 °C / Inert atmosphere

Reference： [1]Matsumoto, Ken; Koide, Naoyuki [Molecular Crystals and Liquid Crystals Science and Technology, Section A: Molecular Crystals and Liquid Crystals, 2001, vol. 365, p. 81 - 89]
[2]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US4748184, 1988, A
[3]Faridoon; Hussein, Waleed M.; Ul Islam, Nazar; Guddat, Luke W.; Schenk, Gerhard; McGeary, Ross P. [Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 7, p. 2555 - 2559]
[4]Current Patent Assignee: SPHAERA PHARMA - WO2014/16849, 2014, A2
[5]Rajasingam, Arison; Schmidt, Rolf; Woo, Simon; DeWolf, Christine; Forgione, Pat [Synthetic Communications, 2014, vol. 44, # 8, p. 1066 - 1075]
[6]Ao, Junli; Chen, Yuanmou; Xu, Xiaoling; Zhang, Xu; Yu, Yue; Yu, Peng; Hua, Erbing [Asian Journal of Chemistry, 2014, vol. 26, # 7, p. 2092 - 2098]
[7]Mulani, Khudbudin B.; Ganjave, Nitin V.; Chavan, Nayaku N. [Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2014, vol. 53, # 5, p. 591 - 596] Manurkar, Nagesh; More, Sayaji; Mulani, Khudbudin; Ganjave, Nitin; Chavan, Nayaku [Journal of Chemical Sciences, 2017, vol. 129, # 9, p. 1461 - 1468]
[8]Dong, Jiajia; Sharpless, K. Barry; Kwisnek, Luke; Oakdale, James S.; Fokin, Valery V. [Angewandte Chemie - International Edition, 2014, vol. 53, # 36, p. 9466 - 9470][Angew. Chem., 2014, vol. 126, # 36, p. 9620 - 9624][Angewandte Chemie, 2014, vol. 126, # 36, p. 9620 - 9624]
[9]Zhang, Xuehong; Lin, Yijie; Liu, Lina; Lin, Cuiwu [Luminescence, 2015, vol. 30, # 3, p. 269 - 279]
[10]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]
[11]Current Patent Assignee: ABBVIE INC - WO2016/4272, 2016, A1
[12]Current Patent Assignee: LG CHEM CO.,LTD. - US2016/145187, 2016, A1
[13]Gokcen, Taner; Gulcin, Ilhami; Ozturk, Turan; Goren, Ahmet C. [Journal of Enzyme Inhibition and Medicinal Chemistry, 2016, vol. 31, p. 180 - 188] Köksal, Zeynep; Kalin, Ramazan; Camadan, Yasemin; Usanmaz, Hande; Almaz, Züleyha; Gülçin, Ilhami; Gokcen, Taner; Gören, Ahmet Ceyhan; Ozdemir, Hasan [Molecules, 2017, vol. 22, # 6]
[14]Guo, Xuliang; Xing, Qingyu; Lei, Kunhua; Zhang-Negrerie, Daisy; Du, Yunfei; Zhao, Kang [Advanced Synthesis and Catalysis, 2017, vol. 359, # 24, p. 4393 - 4398]
[15]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]
[16]Bi, Jingjie; Wang, Wenqing; Du, Junxi; Chen, Kun; Cheng, Kui [European Journal of Medicinal Chemistry, 2019, vol. 179, p. 233 - 245]
[17]Bo, Yong-Xin; Chen, Shi-Wu; Hao, Shu-Yi; Wang, Xing-Rong; Xiang, Rong; Xu, Yu [Bioorganic and medicinal chemistry, 2020, vol. 28, # 5]
[18]Lü, Zirui; Li, Xiaona; Li, Kebin; Wang, Cong; Du, Tingting; Huang, Wei; Ji, Ming; Li, Changhong; Xu, Fengrong; Xu, Ping; Niu, Yan [ACS Medicinal Chemistry Letters, 2021, vol. 12, # 5, p. 696 - 703]
[19]Current Patent Assignee: E SCAPE BIO - WO2021/87292, 2021, A1
[20]Liu, Yanfei; Long, Shuo; Zhang, Shanshan; Tan, Yifu; Wang, Ting; Wu, Yuwei; Jiang, Ting; Liu, Xiaoqin; Peng, Dongming; Liu, Zhenbao [RSC Advances, 2021, vol. 11, # 29, p. 17611 - 17621]

13
[ 27914-73-4 ]
[ 131631-89-5 ]

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

14
[ 27914-73-4 ]
[ 1477-19-6 ]

Reference： [1]Bulletin de la Societe Chimique de France,1959,p. 1682,1685

15
[ 27914-73-4 ]
[ 2979-06-8 ]

Reference： [1]Chemische Berichte,1951,vol. 84,p. 443,450

16
[ 288156-90-1 ]
[ 27914-73-4 ]
C₂₀H₂₂N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With triethylamine In tetrahydrofuran at 20℃; for 64h;	11 Example 11; 4-[3-(4-hydroxybenzamidyl)benzoyl]-1-methylpiperidine hydrochloride 4-acetoxybenzoyl chloride (200 mg, 0.92 mmol) in tetrahydrofuran (10 mL) was added to 4-[3-aminobenzoyl]1-methylpiperidine (200 mg, 0.92 mmol) and triethylamine (0.5 mL, 3.6 mmol) in tetrahydrofuran (10 ml). The reaction mixture was stirred 64 h at room temperature. The reaction mixture was diluted with ethyl acetate and water then extracted with ethyl acetate. The ethyl acetate extracts were washed with water, brine, then dried over sodium sulfate. Solvent was removed under reduced pressure to give 493 mg of product. This product was dissolved in methanol (5 mL) and 5N sodium hydroxide solution (5 mL) and stirred until the hydrolysis of the acetate was complete. The solvent was removed under reduced pressure. The residue was dissolved in water and the pH of the solution was adjusted to 8-9 with 1N hydrochloric acid solution. This solution was extracted with chloroform/isopropanol (3:1) and dried over sodium sulfate. Solvent was removed under reduced pressure to give 270 mg of a foam. [00459] Purification by flash chromatography (silica gel, 5% 2M ammonia in methanol/methylene chloride then 10% 2M ammonia in methanol/methylene chloride) gave 240 mg (77%). Crystallization as the hydrochloric acid salt from ethyl acetate/ethanol provided 220 mg of an off white powder. [00460] Mp>200° C. MS(m/e): 339(M+1), 337(M-1). [00461] Analysis for C20H23ClN2O3: [00462] Calcd: C, 64.08; H, 6.18; N, 7.47; Found: C, 64.27; H, 6.40; N, 7.45.

Reference： [1]Current Patent Assignee: ELI LILLY & CO - US6777428, 2004, B1 Location in patent: Page 34

17
[ 27914-73-4 ]
[ 220150-55-0 ]
[ 443682-67-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	With pyridine In dichloromethane; water	1 (1) (1) Synthesis of p-acetoxybenzoic Acid-(R)-3-ethyl-1-methylpentyl Ester An eggplant type flask was charged with 3.55 g of p-acetoxybenzoyl chloride, 2.12 g of (R)-4-ethyl-2-hexanol and 20 mL of dichloromethane, and these were dissolved. To the resultant solution was added 1.60 mL of pyridine, and the mixture was stirred at room temperature for 1 day. To the resultant reaction mixture was added 20 mL of water, and the mixture was stirred for 30 minutes and then separated into an organic layer and an aqueous layer. The organic layer was washed with 2N hydrochloric acid, with a 1N sodium hydroxide aqueous solution and with water, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, to give 4.77 g of an end compound (crude product yield 100%).
97%	With pyridine In toluene at 20℃; for 15h;	3.2 (2) Synthesis of (R)-4-acetoxy-1-(1-methyl-3-ethylpentyloxycarbonyl)benzene A reactor was charged with 49 g (0.246 mol) of 4-acetoxybenzoyl chloride, 29 g (0.222 mol) of (R)-4-ethyl-2-hexanol and 750 ml of dehydrated toluene, 35 g (0.442 mol) of pyridine was dropwise added thereto, and a mixture was stirred at room temperature for 15 hours. To a reaction solution was added 300 ml of water, a mixture was stirred at room temperature for 1 hour, and then, a liquid of an organic layer was separated. The organic layer was washed with 2N hydrochloric acid, with a 1N sodium hydroxide aqueous solution and with water. The washed organic layer was dried over anhydrous sodium sulfate and filtered. Then, the solvent was distilled off, to give 63 g (0.215 mol, yield 97 %) of an end compound.
92%	With pyridine In water; toluene	30.2 (2) (2) Synthesis of (R)-3-ethyl-1-methylpentyl-4-acetoxybenzoate 10.0 Grams (50.4 mmol) of 4-acetoxybenzoic acid chloride, 6.0 g (46.1 mmol) of (R)-4-ethyl-2-hexanol and 100 ml of toluene were placed in a reactor, 7.3 g (92.1 mmol) of pyridine was dropwise added, and the mixture was stirred at room temperature for 3 hours. To the reaction solution was added 20 ml of water, the mixture was stirred at room temperature for 30 minutes, and a liquid of an organic layer was separated. The organic layer was washed with 2N hydrochloric acid,with a 1N sodium hydroxide aqueous solution and then with water. The organic layer was dried over anhydrous sodium sulfate and filtered, and then the solvent was distilled off, to give 13.5 g of (R)-3-ethyl-1-methylpentyl-4-acetoxybenzoate (yield 92 %).

63 g (0.215 mol. yield 97%)

With pyridine In water; toluene

4.2 (2) (2) Synthesis of (R)-4-acetoxy-1-(3-ethyl-1-methylpentyloxycarbonyl)benzene 49 Grams (0.246 mol) of 4-acetoxybenzoyl chloride, 29 g (0.222 mol) of (R)-4-ethyl-2-hexanol and 750 ml of dehydrated toluene were placed in a reactor, 35 g (0.442 mol) of pyridine was dropwise added thereto, and the mixture was stirred at room temperature for 15 hours. To the reaction solution was added 300 ml of water, and the mixture was stirred at room temperature for 1 hour, followed by separating of the reaction mixture into two organic layers of liquid. The obtained organic layer was washed with 2N hydrochloric acid, washed with a 1N sodium hydroxide aqueous solution and then washed with water. The washed organic layer was dried over anhydrous sodium sulfate and filtered, and the solvent was removed from the filtrate by distillation, to give 63 g (0.215 mol. yield 97%) of an end compound.

Reference： [1]Current Patent Assignee: MITSUBISHI GAS CHEMICAL COMPANY INC - US2003/102459, 2003, A1
[2]Current Patent Assignee: MITSUBISHI GAS CHEMICAL COMPANY INC - EP1380567, 2004, A1 Location in patent: Page 6
[3]Current Patent Assignee: MITSUBISHI GAS CHEMICAL COMPANY INC - EP1225212, 2002, A1
[4]Current Patent Assignee: MITSUBISHI GAS CHEMICAL COMPANY INC - US2003/54119, 2003, A1

18
[ 27914-73-4 ]
[ 220150-55-0 ]
(R)-3-ethyl-1-methylpentyl-4-acetoxybenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With pyridine In toluene at 20℃; for 3h;	30.2 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; (2) Synthesis of (R)-3-ethyl-1-methylpentyl-4-acetoxybenzoate 10.0 Grams (50.4 mmol) of 4-acetoxybenzoic acid chloride, 6.0 g (46.1 mmol) of (R)-4-ethyl-2-hexanol and 100 ml of toluene were placed in a reactor, 7.3 g (92.1 mmol) of pyridine was dropwise added, and the mixture was stirred at room temperature for 3 hours. [00133] To the reaction solution was added 20 ml of water, the mixture was stirred at room temperature for 30 minutes, and a liquid of an organic layer was separated. The organic layer was washed with 2N hydrochloric acid, with a 1N sodium hydroxide aqueous solution and then with water. The organic layer was dried over anhydrous sodium sulfate and filtered, and then the solvent was distilled off, to give 13.5 g of (R)-3-ethyl-1-methylpentyl-4-acetoxybenzoate (yield 92%).

Reference： [1]Current Patent Assignee: MITSUBISHI GAS CHEMICAL COMPANY INC - US6677475, 2004, B2 Location in patent: Page column 14

19
[ 27914-73-4 ]
[ 2687-43-6 ]
4-((benzyloxy)carbamoyl)phenyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium hydrogencarbonate In tetrahydrofuran at 20℃; for 1h;	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).

Reference： [1]Current Patent Assignee: ONXEO - WO2004/65354, 2004, A1 Location in patent: Page 126; 78; 85

20
[ 27914-73-4 ]
[ 84449-65-0 ]
[ 166975-60-6 ]

Yield	Reaction Conditions	Operation in experiment
	With trifluorormethanesulfonic acid; In dichloromethane; for 16h;Heating / reflux;	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) delta7.70(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).

Reference： [1]Patent: US6756388,2004,B1 .Location in patent: Page/Page column 48

21
[ 27914-73-4 ]
(R)-2-nonanol [ No CAS ]
[ 479629-72-6 ]

Yield	Reaction Conditions	Operation in experiment
100%	With pyridine In dichloromethane; water	9.1 (1) (1) Synthesis of p-acetoxybenzoic Acid-(R)-2-nonyl Ester An eggplant type flask was charged with 5.00 g of p-acetoxybenzoyl chloride, 3.00 g of (R)-2-nonanol and 20 mL of dichloromethane, and these were dissolved. To the resultant solution was added 3.00 mL of pyridine, and the mixture was stirred at room temperature for 1 day. To the reaction mixture was added 20 mL of water, and the mixture was stirred for 30 minutes and separated into an organic layer and an aqueous layer. The organic layer was washed with 2N hydrochloric acid, with a 1N sodium hydroxide aqueous solution and with water, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, to give 6.37 g of an end compound (crude product yield 100%).

Reference： [1]Current Patent Assignee: MITSUBISHI GAS CHEMICAL COMPANY INC - US2003/102459, 2003, A1

22
[ 27914-73-4 ]
methyl 4-amino-5-cyclohexylaminothiophene-2-carboxylate [ No CAS ]
[ 852700-18-6 ]

Yield	Reaction Conditions	Operation in experiment
53%	With pyridine In chloroform at 0℃; for 0.25h;	1.6 Step 6: Production of methyl 4-(4-acetoxybenzoylamino)-5-cyclohexylaminothiophene-2-carboxylate To a solution of methyl 4-amino-5-cyclohexylaminothiophene-2-carboxylate obtained in Step 5 in pyridine (10 ml) was added dropwise under ice-cooling a solution of 4-acetoxybenzoyl chloride obtained in Step 4 in chloroform (10 ml), and the mixture was stirred for 15 min. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1-3:2) to give methyl 4-(4-acetoxybenzoylamino)-5-cyclohexylaminothiophene-2-carboxylate (2.29 g, yield 53%). 1H-NMR(400MHz, δppm, DMSO-d6): 9.66(1H, s), 7.97 (2H, d, J=8.0Hz), 7.68(1H, s), 7.27(2H, d, J=8.0Hz), 6.62(2H, d, J=8.0Hz), 3.71(3H, s), 3.07(1H, brs), 2.30(3H, s), 1.97-2.04(2H, m), 1.69-1. 77 (2H, m), 1.55-1.64(1H, m), 1.11-1.39(5H, m).

Reference： [1]Current Patent Assignee: JAPAN TOBACCO INC - EP1688420, 2006, A1 Location in patent: Page/Page column 123-124

23
[ 27914-73-4 ]
[ 36801-01-1 ]
[ 104457-09-2 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; dmap In dichloromethane	7 S-(4-Cyanophenyl) 4-(acetoxy)thiobenzoate EXAMPLE 7 S-(4-Cyanophenyl) 4-(acetoxy)thiobenzoate A solution of 4-acetoxybenzoyl chloride (3.33 g) in dry dichloromethane (20 ml) was added over 10 minutes to a cool (5° C.), stirred solution of 4-cyanothiophenol (2.06 g), pyridine (1.45 ml) and 4-N,N-dimethylaminopyridine (25 mg) in dry dichloromethane (30 ml). The stirred solution was allowed to reach room temperature overnight and the organic solution was washed successively with aqueous 2M hydrochloric acid, a saturated sodium bicarbonate solution and water. Evaporation of the extracts, which had been dried over magnesium sulphate, afforded the desired thioester (4.53 g). νmax (Nujol mull) 2220, 1757, 1672 cm-1.

Reference： [1]Current Patent Assignee: SANOFI; HOESCHT UK - US4849419, 1989, A

24
[ 27914-73-4 ]
1'-[(3S)-3-(3,4-dichlorophenyl)-4-(methylamino)butyl]-N,N-dimethyl-1,4'-bipiperidine-4'-carboxamide hydrochloride [ No CAS ]
4-([(2S)-2-(3,4-dichlorophenyl)-4-{4'-[(-N,N-dimethylamino)-carbonyl]1,4'-bipiperidin-1'-yl}butyl](methyl)amino}carbonyl)phenyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	Stage #1: 4-acetoxybenzoyl chloride; 1'-[(3S)-3-(3,4-dichlorophenyl)-4-(methylamino)butyl]-N,N-dimethyl-1,4'-bipiperidine-4'-carboxamide hydrochloride With triethylamine In dichloromethane at 20℃; for 15h; Stage #2: With potassium hydroxide In tert-butyl methyl ether; water; ethyl acetate	14 220 mg (0.00038 mol) of 1 '-[(3S)-3-(3,4-dichlorophenyl)-4-(methylamino)butyl]-?/,?/- dimethyl-1 ,4'-bipiperidine-4'-carboxamide were dissolved in 20 ml of methylene chloride in the presence of 200 μl of triethylamine under stirring at room temperature. To the reaction mixture, were added drop wise at room temperature, a solution of 98 mg of 4-acetoxybenzoyl chloride in 20 ml of methylene chloride and subsequently 200 μl of triethylamine were added. The reaction mixture was stirred for 15 hours at room temperature and concentrated in vacuum. The residue was dissolved in 50 ml of ethyl acetate and 30 ml of MTBE in the presence of 200 mg potassium hydroxide dissolved in 20 ml of water. The organic phase was separated and washed 4 times with 20 ml of water. The organic layer was recovered, dried on sodium sulphate and concentrated to dryness to deliver 240 mg (quantitative yield) of 4-([(2S)-2-(3,4-dichlorophenyl)-4-{4'- [(dimethylaminoJcarbonyll-i ^'-bipiperidin-i '-ylJbuty^methyOaminoJcarbonyOphenyl acetate as a glassy material.1HNMR(as base) (500 MHz, CDCI3 ) d: 7.45-7.1 (m, 7H), 7.0, 6.8 (2xbs, 0.7H), 3.82 (bs, 0.7H), 3.55 (dd, 1 H), 3.5-3.2 (m, 4 H), 3.1 (bs, 0.7 H), 3.0 (m, 2H), 2.95-2.90 (2xs, 3H), 2.8-2.5 (m, 4.5H),2.3 (s, 3H) 2.25-1.6 (m, 12H), 1.5 (s, 4H), 1 ,4 (s, 2H). 13CNMR (125MHz, CDCI3 ) d: 170.7, 168.2, 150.7, 131.7., 121.5, 120.9, 66.1 , 55.2, 56.1 , 52.6, 51.7, 50.9, 50.4, 46.6, 40.9, 38.0, 36.9, 29.9, 26.2, 24.4, 20.4 LC-MS: M+1 (monoisotope): 631. Retention time: 7.78 min (API).

Reference： [1]Current Patent Assignee: ABBVIE INC - WO2007/88181, 2007, A1 Location in patent: Page/Page column 72-73

25
[ 27914-73-4 ]
1-(2',3',4',5'-Tetra-O-acetyl-β-D-glucopyranosyl)urea [ No CAS ]
[ 1050350-24-7 ]

Yield	Reaction Conditions	Operation in experiment
72%	With zinc(II) chloride In chloroform Heating;
72%	With zinc(II) chloride In chloroform for 24h; Reflux;	N-(4-Acetoxybenzoyl)-N’-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)urea 23 General procedure: Method A (adapted from lit.3): To a solution of an acyl chloride (7.7 mmol) in 20 ml of dry chloroform anhydrous zinc chloride (80 mg, 0.59 mmol) and 2,3,4,6-tetra-O-acetyl--d-glucopyranosyl urea (16, 1 g, 2.56 mmol) were added with stirring. The reaction mixture was refluxed until TLC showed the complete transformation of 16. Then the reaction mixture was poured into ice-water and was extracted with chloroform (2x). The organic phases were collected and washed with satd. aq. Na2CO3 solution and water. After drying the solvent was evaporated and the residue was purified by column chromatography (eluent: EtOAc : hexane = 1:2).

Reference： [1]Somsak, Laszlo; Felfoeldi, Nora; Konya, Balint; Huese, Csaba; Telepo, Katalin; Bokor, Eva; Czifrak, Katalin [Carbohydrate Research, 2008, vol. 343, # 12, p. 2083 - 2093]
[2]Nagy, Veronika; Felfoeldi, Nora; Konya, Balint; Praly, Jean-Pierre; Docsa, Tibor; Gergely, Pal; Chrysina, Evangelia D.; Tiraidis, Costas; Kosmopoulou, Magda N.; Alexacou, Kyra-Melinda; Konstantakaki, Maria; Leonidas, Demetres D.; Zographos, Spyros E.; Oikonomakos, Nikos G.; Kozmon, Stanislav; Tvaroska, Igor; Somsak, Laszlo [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 5, p. 1801 - 1816]

26
[ 27914-73-4 ]
[ 1109286-11-4 ]
[ 1109285-83-7 ]

Yield	Reaction Conditions	Operation in experiment
63%	With triethylamine In tetrahydrofuran at 20℃;	5.3 Into a solution of 510 (0.815 g, 4.10 mmol) and dry THF (20.0 mL) was added a solution of triethylamine (0.572 mL, 4.10 mmol) and dry THF (5.00 mL), followed by a solution of 508 (0.500 g, 3.42 mmol) dissolved in dry THF (15.0 mL). The reaction was stirred at room temperature. After stirring overnight, the reaction was concentrated in vacuo. The residue was partitioned between a saturated aqueous sodium bicarbonate and dichloromethane. The dichloromethane layer was washed a second time with the saturated sodium bicarbonate solution and than twice with aq. 1 M HCl. The dichloromethane layer was dried over anhydrous magnesium sulfate and concentrated in vacuo to give crude 82 (1.15 g,>100%) as a brown solid. The crude product was suspended in diethyl ether, stirred and filtered. The filter pad was washed with ether several times, and dried in vacuo to give 82 (0.692 g, 63%) as a light brown solid.Data for 82: mp=185.7-188.7° C.; 1H-NMR (400 MHz, DMSO-d6) δ 12.8 (s, 1 H), 8.14 (d, J=8.9 Hz, 2 H), 7.32 (d, J=8.9 Hz, 2 H), 6.89 (s, 1 H), 2.50 (s, 3 H), 2.31 (s, 3 H) ppm; MS (ESI+) m/z (rel. intensity): 100.1 (37), 122.2 (98.3), 163.2 (49), 309.2 (100), 331.2 (29) m/z. MS (ESI-) m/z (rel. intensity): 111.0 (16), 203.2 (31), 307.2 (100).
63%	With triethylamine In tetrahydrofuran at 20℃;	1.5.2.3 Into a solution of 510 (0.815 g, 4.10 mmol) and dry THF (20.0 mL) was added a solution of triethylamine (0.572 mL, 4.10 mmol) and dry THF (5.00 mL), followed by a solution of 508 (0.500 g, 3.42 mmol) dissolved in dry THF (15.0 mL). The reaction was stirred at room temperature. After stirring overnight, the reaction was concentrated in vacuo. The residue was partitioned between a saturated aqueous sodium bicarbonate and dichloromethane. The dichloromethane layer was washed a second time with the saturated sodium bicarbonate solution and than twice with aq. 1 M HCl. The dichloromethane layer was dried over anhydrous magnesium sulfate and concentrated in vacuo to give crude 512 (1.15 g, >100%) as a brown solid. The crude product was suspended in diethyl ether, stirred and filtered. The filter pad was washed with ether several times, and dried in vacuo to give 512 (0.692 g, 63%) as a light brown solid. Data for 512: mp=185.7-188.7° C.; 1H-NMR (400 MHz, DMSO-d6) δ 12.8 (s, 1H), 8.14 (d, J=8.9 Hz, 2H), 7.32 (d, J=8.9 Hz, 2H), 6.89 (s, 1H), 2.50 (s, 3H), 2.31 (s, 3H) ppm; MS (ESI+) m/z (rel. intensity): 100.1 (37), 122.2 (98.3), 163.2 (49), 309.2 (100), 331.2 (29) m/z. MS (ESI-) m/z (rel. intensity): 111.0 (16), 203.2 (31), 307.2 (100).

Reference： [1]Current Patent Assignee: ROMARK LABORATORIES, L.C. - US2009/36467, 2009, A1 Location in patent: Page/Page column 75-76
[2]Current Patent Assignee: ROMARK LABORATORIES, L.C. - US2012/108591, 2012, A1 Location in patent: Page/Page column 31

27
[ 27914-73-4 ]
[ 1169389-56-3 ]
[ 1169389-75-6 ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: 4-acetoxybenzoyl chloride; 4-(5-(4-tert-butylphenyl)-1,3,4-oxadiazol-2-yl)benzoylhydrazine In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 19h; Stage #2: With pyridine In tetrahydrofuran; N,N-dimethyl-formamide for 1.5h;	6.1 Step 1: 4-(2-(4-(5-(4-tert-butylphenyl)-l,3,4-oxadiazol-2- yl)benzoyl)hydrazinecarbonyl)phenyl acetate (YZ -1-243):To a solution of 4 -(5-(4-tert-butylphenyl)-l,3,4-oxadiazol-2-yl)benzohydrazine (2.0 g, 5.95 mmol) in dry tetrahydrofuran (80.0 ml) and DMF (7.0 ml), was slowly added 4 -(chlorocarbonyl)phenyl acetate (1.3 g, 6.55 mmol) at room temperature. During addition of 4 -(chlorocarbonyl)phenyl acetate, white solids appeared. The reaction mixture was stirred for 19 hours and then pyridine (10.0 ml) was added and stirred for another 1.5 hours. Next, water (300.0 ml) was added. The yellow solid was collected by filtration and dried overnight under vacuum and provided 2.70 g(90.0 %) in yield.1H NMR (400 MHz, DMSO -de) δ: 10.79 (s, 1 H, NH), 10.64 (s, 1 H, NH), 8.28 (d, 2H, J= 8.4 Hz), 8.15 (d, 2 H, J= 8.4 Hz), 8.08 (d, 2 H, J= 8.0 Hz), 7.97 (d, 2 H, J = 8.8 Hz), 7.66 (d, 2 H, J= 8.4 Hz), 7.30 (d, 2 H, J= 8.8 Hz), 2.31 (s, 3 H, CH 3), 1.33(s, 9 H, 3 x CH3) ppm.

Reference： [1]Current Patent Assignee: GEORGIA INSTITUTE OF TECHNOLOGY - WO2009/80797, 2009, A1 Location in patent: Page/Page column 41-42

28
[ 27914-73-4 ]
[ 1169389-62-1 ]
[ 1169389-79-0 ]

Yield	Reaction Conditions	Operation in experiment
90.9%	Stage #1: 4-acetoxybenzoyl chloride; 3-(5-(4-tert-butylphenyl)-1,3,4-oxadiazol-2-yl)benzohydrazide In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 18h; Stage #2: With pyridine In tetrahydrofuran; N,N-dimethyl-formamide for 1h;	7.1 Step 1 : 4-(2-(3-(5-(4-tert-butylphenyl)-1.3.4-oxadiazol-2- yl)benzoyl)hydrazinecarbonyl)phenyl acet ate (YZ -1-237):To a solution of 3 -(5-(4-tert-butylphenyl)-l,3,4-oxadiazol-2-yl)benzo- hydrazine (2.0 g, 5.95 mmol) in dry tetrahydrofuran (100.0 ml) and DMF (5.0 ml), was slowly added methyl 4 -(chlorocarbonyl)phenyl acetate (1.3 g, 6.54 mmol) at room temperature under nitrogen. During the addition of methyl 3 - (chlorocarbonyl)phenyl acetate, white solids appeared. The reaction mixture was stirred at room temperature for 18 hours and then pyridine (10.0 ml) was added and stirred for another hour. Then, wat er (300.0 ml) was added into the reaction mixture. The white solid was collected by filtration and dried overnight under vacuum and provided 2.7 g (90.9 %) yield.1H NMR (400 MHz, DMSO -d6) δ: 10.88 (s, br, 2 H, 2 x NH), 8.52 (t, I H, J= 1.6 Hz), 8.22 (dt, 2 H, J1 = 7.6 Hz, J2 = 1.6 Hz), 8.05 (m, 4 H), 7.71 (t, 1 H, J = 7.6 Hz) 7.65 (m, 4 H), 2.49 (s, 3 H, CH 3), 1.33 (s, 9 H, 3 x CH 3) ppm.

Reference： [1]Current Patent Assignee: GEORGIA INSTITUTE OF TECHNOLOGY - WO2009/80797, 2009, A1 Location in patent: Page/Page column 44

29
[ 27914-73-4 ]
[ 1859-75-2 ]
[ 1319210-04-2 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 5722 - 5736

30
[ 27914-73-4 ]
[ 1446439-62-8 ]
[ 1446439-73-1 ]

Yield	Reaction Conditions	Operation in experiment
38%	With dmap; triethylamine In dichloromethane at 20 - 40℃; Cooling with ice;	4.1.6 General synthetic procedure for diacylhydrazine derivatives 2a-2m and 3a-3c General procedure: A mixture of 7 (1mmol), triethylamine (1.5mmol) and 4-dimethylaminopyridine (0.05mmol) in anhydrous CH2Cl2 (10mL) was stirred in an ice bath, and substituted benzoyl chloride (1.1mmol) in CH2Cl2 (5mL) was added. After stirring for 3h at room temperature and another 2-5h at 35-40°C, the reaction mixture was extracted with CHCl3. The combined organic layer was washed with aqueous sodium bicarbonate, brine and water, and then dried over anhydrous magnesium sulfate. After evaporated, the residue was purified by silica gel column chromatography by petroleum ether/ethyl acetate to afford the target compounds 2a-2m.34,16 And then, the products 2j, 2l, and 2m were deacetylation to give the target compounds 3a-3c. Their physico-chemical properties and the spectral data are provided in Supplementary data.

Reference： [1]Liu, Xiu; Zhang, Ling; Tan, Jin-Guo; Xu, Han-Hong [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 15, p. 4687 - 4697]

31
[ 27914-73-4 ]
[ 1446439-63-9 ]
[ 1446439-74-2 ]

Yield	Reaction Conditions	Operation in experiment
25%	With dmap; triethylamine In dichloromethane at 20 - 40℃; Cooling with ice;	4.1.6 General synthetic procedure for diacylhydrazine derivatives 2a-2m and 3a-3c General procedure: A mixture of 7 (1mmol), triethylamine (1.5mmol) and 4-dimethylaminopyridine (0.05mmol) in anhydrous CH2Cl2 (10mL) was stirred in an ice bath, and substituted benzoyl chloride (1.1mmol) in CH2Cl2 (5mL) was added. After stirring for 3h at room temperature and another 2-5h at 35-40°C, the reaction mixture was extracted with CHCl3. The combined organic layer was washed with aqueous sodium bicarbonate, brine and water, and then dried over anhydrous magnesium sulfate. After evaporated, the residue was purified by silica gel column chromatography by petroleum ether/ethyl acetate to afford the target compounds 2a-2m.34,16 And then, the products 2j, 2l, and 2m were deacetylation to give the target compounds 3a-3c. Their physico-chemical properties and the spectral data are provided in Supplementary data.

Reference： [1]Liu, Xiu; Zhang, Ling; Tan, Jin-Guo; Xu, Han-Hong [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 15, p. 4687 - 4697]

32
[ 27914-73-4 ]
[ 1446439-64-0 ]
[ 1446439-76-4 ]

Yield	Reaction Conditions	Operation in experiment
26%	With dmap; triethylamine In dichloromethane at 20 - 40℃; Cooling with ice;	4.1.6 General synthetic procedure for diacylhydrazine derivatives 2a-2m and 3a-3c General procedure: A mixture of 7 (1mmol), triethylamine (1.5mmol) and 4-dimethylaminopyridine (0.05mmol) in anhydrous CH2Cl2 (10mL) was stirred in an ice bath, and substituted benzoyl chloride (1.1mmol) in CH2Cl2 (5mL) was added. After stirring for 3h at room temperature and another 2-5h at 35-40°C, the reaction mixture was extracted with CHCl3. The combined organic layer was washed with aqueous sodium bicarbonate, brine and water, and then dried over anhydrous magnesium sulfate. After evaporated, the residue was purified by silica gel column chromatography by petroleum ether/ethyl acetate to afford the target compounds 2a-2m.34,16 And then, the products 2j, 2l, and 2m were deacetylation to give the target compounds 3a-3c. Their physico-chemical properties and the spectral data are provided in Supplementary data.

Reference： [1]Liu, Xiu; Zhang, Ling; Tan, Jin-Guo; Xu, Han-Hong [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 15, p. 4687 - 4697]

33
[ 27914-73-4 ]
[ 1446439-65-1 ]
[ 1446439-77-5 ]

Yield	Reaction Conditions	Operation in experiment
27%	With dmap; triethylamine In dichloromethane at 20 - 40℃; Cooling with ice;	4.1.6 General synthetic procedure for diacylhydrazine derivatives 2a-2m and 3a-3c General procedure: A mixture of 7 (1mmol), triethylamine (1.5mmol) and 4-dimethylaminopyridine (0.05mmol) in anhydrous CH2Cl2 (10mL) was stirred in an ice bath, and substituted benzoyl chloride (1.1mmol) in CH2Cl2 (5mL) was added. After stirring for 3h at room temperature and another 2-5h at 35-40°C, the reaction mixture was extracted with CHCl3. The combined organic layer was washed with aqueous sodium bicarbonate, brine and water, and then dried over anhydrous magnesium sulfate. After evaporated, the residue was purified by silica gel column chromatography by petroleum ether/ethyl acetate to afford the target compounds 2a-2m.34,16 And then, the products 2j, 2l, and 2m were deacetylation to give the target compounds 3a-3c. Their physico-chemical properties and the spectral data are provided in Supplementary data.

Reference： [1]Liu, Xiu; Zhang, Ling; Tan, Jin-Guo; Xu, Han-Hong [Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 15, p. 4687 - 4697]

34
[ 27914-73-4 ]
N¹-tosyl-C-(2,3,4,6-tetra-O-benzoyl-β-d-glucopyranosyl)formamidrazone [ No CAS ]
C₅₁H₄₁N₃O₁₃S [ No CAS ]
5-(4-acetoxyphenyl)-3-(2',3',4',6'-tetra-O-benzoyl-β-d-glucopyranosyl)-1,2,4-triazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	Stage #1: 4-acetoxybenzoyl chloride; N¹-tosyl-C-(2,3,4,6-tetra-O-benzoyl-β-d-glucopyranosyl)formamidrazone With pyridine In chloroform at 20℃; for 48h; Cooling with ice; Stage #2: C₅₁H₄₁N₃O₁₃S With tetrabutyl ammonium fluoride In tetrahydrofuran for 3h; Reflux;	B.10 4.4.10 5-(4-Acetoxyphenyl)-3-(2',3',4',6'-tetra-O-benzoyl-β-d-glucopyranosyl)-1,2,4-triazole (11f). 4.4.4 General procedure V for the synthesis of 5-substituted-3-(2′,3′,4′,6′-tetra-O-benzoyl-β-d-glucopyranosyl)-1,2,4-triazoles (11) from N1-tosyl-C-(2,3,4,6-tetra-O-benzoyl-β-d-glucopyranosyl)formamidrazone (4). N1-Tosyl-C-(2,3,4,6-tetra-O-benzoyl-β-d-glucopyranosyl)formamidrazone (4, 0.50 g, 0.63 mmol) was dissolved in anhydrous CHCl3 (10 mL) and anhydrous pyridine (92 μL, 1.14 mmol, 1.8 equiv) was added. The mixture was cooled in an ice bath, and a solution of an acid chloride (0.95 mmol, 1.5 equiv) in anhydrous CHCl3 (5 mL) was added dropwise over 15 min. Subsequently the mixture was stirred at rt and monitored by TLC (1:1 EtOAc/hexane). After total consumption of the starting material (2 days) the mixture was diluted with CHCl3 (15 mL) and extracted with water (2×15 mL). The organic phase was dried over MgSO4, concentrated under diminished pressure, and the crude product was purified by column chromatography. From tosyl-amidrazone 4 (0.20 g, 0.25 mmol) and 4-acetoxybenzoyl chloride (75 mg, 0.38 mmol) according to general procedure V. After extraction and evaporation the crude mixture was dissolved in THF (6 mL), 1 M solution of Bu4NF in THF (0.50 mL) was added and the mixture was refluxed for 3 h, then the solvent was removed under diminished pressure. The residue was purified by column chromatography (1:4 EtOAc/toluene) to yield 0.12 g (60%) white amorphous solid. Rf: 0.33 (1:3 EtOAc/toluene); [α]D -8 (c 0.11, CHCl3); 1H NMR (CDCl3) δ (ppm): 7.93 (2H, d, J=8.0 Hz, aromatics), 7.90-7.87 (4H, m, aromatics), 7.81 (2H, d, J=7.4 Hz, aromatics), 7.74 (2H, d, J=8.0 Hz, aromatics), 7.42 (1H, t, J=7.3 Hz, aromatics), 7.35-7.06 (11H, m, aromatics), 6.98 (2H, J=8.6 Hz, aromatics), 6.37, 6.21, 6.05 (3*1H, 3 pseudo t, J=9.9, 9.2 Hz in each, H-2', H-3', H-4'), 5.40 (1H, d, J=9.9 Hz, H-1'), 4.62 (2H, m, H-6'a, H-6'b), 4.48 (1H, ddd, J=9.9, 5.5, 4.3 Hz, H-5'), 2.21 (3H, s, CH3); 13C NMR (CDCl3) δ (ppm): 169.1, 166.2, 165.9, 165.1, 165.0 (C=O), 157.7, 156.9 (triazole C-3, C-5), 151.7, 133.2-132.8, 129.7-129.4, 129.0, 128.8, 128.8, 128.6, 128.5, 128.2-127.6, 125.3, 125.1, 121.7 (aromatics), 76.5, 74.4, 74.0, 71.3, 69.5 (C-1'-C-5'), 63.2 (C-6'), 20.8 (CH3). Anal. Calcd for C44H35N3O11 (781.76): C, 67.60; H, 4.51; N, 5.38. Found: C, 67.69; H, 4.62; N, 5.26.

Reference： [1]Bokor, Éva; Fekete, Attila; Varga, Gergely; Szocs, Béla; Czifrák, Katalin; Komáromi, István; Somsák, László [Tetrahedron, 2013, vol. 69, # 48, p. 10391 - 10404]

35
[ 27914-73-4 ]
[ 20876-99-7 ]

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

36
[ 27914-73-4 ]
[ 1415680-12-4 ]
[ 1590385-35-5 ]

Yield	Reaction Conditions	Operation in experiment
52%	With pyridine In chloroform at 20℃; for 24h;	5 3.5.5. 2-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyloxy)-5-acetoxy benzyl (4-acetoxy) benzoate (11) 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. 3.5.5 2-(2,3,4,6-Tetra-O-acetyl-β-d-glucopyranosyloxy)-5-acetoxy benzyl (4-acetoxy) benzoate (11) The compound 11 was obtained from 4-acetoxy benzoyl chloride and glycoside 4. Yield 52%, mp 93-94°C. UV λmax (EtOH)/nm: 232, 274. IR (KBr, νmax/cm-1): 1750, 1640, 1600, 1500, 1370, 1210, 1190, 1030, 906. 1H NMR (CDCl3, 300MHz) δ: 2.03, 2.04, 2.07, 2.10, 2.28, 2.32 (s, 6×3H, Ac), 3.81-3.86 (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), 5.02 (d, 1, J=7.2Hz H-1′), 5.14 (m, 1, H-4′), 5.20-5.41 (m, 2, H-2′, -3′), 5.28 (m, 2H, H-7), 7.02 (dd, 1H, J=2.7, 8.7Hz, H-3), 7.08. 13C NMR (CDCl3, 75.5MHz) δ: 20.5, 21.1 (6×C3, Ac), 60.9 (C2, C6′), 61.7 (CH2, C-7), 68.1 (C, C-4′), 70.9 (C, C-2′), 72.0 (C, C-3′), 72.5 (C, C-5′), 99.7 (C, C-1′), 117.1 (CH, C-2), 121.6 (2×C, C-11, C-13), 121.8 (CH, C-3), 122.1 (CH, C-5), 127.5 (C, C-9), 127.8 (C, C-6), 131.2 (2×CH, C-10, C-14), 146.2 (C, C-4), 151.5 (C, C-1), 154.3 (C, C-12), 165.0 (C=O, C-8), 168.7, 169.2, 169.5, 170.1, 170.5 (6×C=O, Ac). Anal. Calcd for C32H33O16: C, 56.97; H, 5.08. Found: C, 56.81; H, 5.01.

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

37
[ 27914-73-4 ]
[ 615-67-8 ]
C₂₄H₁₇ClO₈ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With pyridine; In 1,2-dichloro-ethane; at 20℃; for 48h;Inert atmosphere;	Three-necked 500 mL round bottom flask wasequipped with magnetic stirrer, nitrogen inlet and calciumchloride guard tube. To the reaction flask, 2-chloro hydroquinone(5.78 g, 0.04 mole) and pyridine (25 mL, 0.3 mole)were added and stirred till dissolution. In another flask, 4-acetoxy benzoyl chloride (23.82 g, 0.12 mole) and 300 mLdry 1,2-dichloroethane were placed and the acid chloridesolution was added to the reaction mixture of 2-<strong>[615-67-8]chlorohydroquinone</strong>solution. This reaction mixture was stirredunder nitrogen blanket for 48 h at room temperature. Thereaction mixture was then washed sequentially with 5%sodium carbonate solution,5%hydrochloric acid and distilledwater. 1,2-Dichloroethane layer was evaporated to dryness onrotavapor. The crude product obtainedwas recrystallised fromchloroform/petroleum ether [60:80] solvent mixture and driedin vacuum oven at 80C for 4 h. Yield 90%.M. p.: 181C, IR(Nujol, cm-1): 1740 (C=O stretching), 760 (C-H bending).1HNMR(CDCl3,delta): 2.3 (s, 6H); 7.1 (m, 6H); 7.3 (d, 1H); 8.2(dd, 4H).

Reference： [1]Journal of Chemical Sciences,2017,vol. 129,p. 1461 - 1468
[2]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2014,vol. 53,p. 591 - 596

38
[ 27914-73-4 ]
1-[3-O-benzoyl-2-O-(2,3,5-tri-O-benzyl-α-D-ribofuranosyl)-β-D-ribofuranosyl]uracil [ No CAS ]
1-[3-O-benzoyl-5-(4-acetoxybenzoyl)-2-O-(2,3,5-tri-O-benzyl-α-D-ribofuranosyl)-β-D-ribofuranosyl]uracil [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	Stage #1: 1-[3-O-benzoyl-2-O-(2,3,5-tri-O-benzyl-α-D-ribofuranosyl)-β-D-ribofuranosyl]uracil With dmap; triethylamine In dichloromethane at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: 4-acetoxybenzoyl chloride In dichloromethane at 0℃; for 0.25h; Inert atmosphere;	Synthesis of 1-[3-O-benzoyl-5-(4-acetoxybenzoyl)-2-O-(2,3,5-tri-O-benzyl-α-D-ribofuranosyl)-β-D-ribofuranosyl]uracil (10) To a solution of 8 (148 mg, 200 lmol) in anhydrous CH2Cl2(4 mL) at 0 C under N2 were added Et3N (40 lL, 0.29 mmol) andcatalytic DMAP (2.2 mg, 0.1 equiv). After 5 min, 4-acetoxybenzoylchloride (9, 51 mg, 0.25 mmol) was added and the mixture wasstirred for 15 min at 0 C. Then, the solvents were evaporatedunder reduced pressure and the residue was purified by silica gelchromatography (hexanes-EtOAc 3:2) to give 10 (134 mg, 75%)as a colorless oil: Rf 0.35 (hexanes-EtOAc 5:5); [a]D20 +77.36 (c1.0, CHCl3); 1H NMR (400 MHz, CDCl3) d 8.20 (br s, 1H, NH), 8.06(d, 2H, J 7.8 Hz, CHBz), 8.05 (d, 2H, J 8.6 Hz, H-2000, H-6000), 7.52 (t,1H, J 7.5 Hz, CHBz), 7.37 (d, 1H, J6,5 8.3 Hz, H-6), 7.36-7.21 (m,15H, H-Ph, CHBz), 7.19 (d, 2H, J 8.5 Hz, H-3000 , H-5000), 7.11-7.09(m, 2H, CHBz), 5.93 (br s, 1H, H-10), 5.49 (d, 1H, J5,6 8.2 Hz, H-5),5.35 (t, 1H, J 6.5 Hz, H-30), 5.31 (d, 1H, J100,200 3.9 Hz, H-100), 4.82-4.73 (m, 3H, H-20 , H-50a, H-40), 4.67 (d, 1H, J 12.1 Hz, OCHPh),4.60-4.53 (m, 2H, OCHPh, H-50b), 4.50 (d, 1H, J 12.0 Hz, OCHPh),4.40 (d, 1H, J 12.3 Hz, OCHPh), 4.31 (d, 1H, J 12.0 Hz, OCHPh),4.22 (d, 1H, J 12.1 Hz, OCHPh), 3.95 (br s, 1H, H-400), 3.85-3.77(m, 2H, H-200 , H-300), 3.06 (dd, 1H, J500a,500b 10.7, J500a,400 3.0 Hz, H-500a), 3.01 (dd, 1H, J500b,500a 10.3, J500b,400 3.9 Hz, H-500b), 2.33 (s, 3H,COCH3); 13C NMR (100 MHz, CDCl3) d 168.7 (COAc), 165.7 (COBz),165.2 (C-7000), 162.4 (C-4), 154.7 (C-4000), 149.6 (C-2), 139.8 (C-6),138.3, 137.8, 137.7 (C-Bn), 133.4 (CHBz), 131.2 (C-2000 , C-6000),130.0 (CHBz), 128.4 (CHBn), 128.4 (CHBz), 128.3, 128.2,127.9, 127.9, 127.7, 127.6, 127.0, 127.5 (CHBn), 126.6 (C-1000),121.9 (C-3000 , C-5000), 102.2 (C-5), 101.6 (C-100), 91.1 (C-10), 82.6 (C-400), 79.2 (C-40), 78.3 (C-200), 78.2 (C-20), 75.4 (C-300), 73.2, 72.5,72.1 (OCH2Ph), 70.8 (C-30), 69.5 (C-500), 62.8 (C-50), 21.2 (COCH3);HRMS: calcd for C51H49N2O14Na [M+Na]+ 913.3178, found913.3185.

Reference： [1]Sylla, Balla; Gauthier, Charles; Legault, Jean; Fleury, Pierre-Yves; Lavoie, Serge; Mshvildadze, Vakhtang; Muzashvili, Tamar; Kemertelidze, Eter; Pichette, André [Carbohydrate Research, 2014, vol. 398, p. 80 - 89]

39
[ 27914-73-4 ]
[ 152460-10-1 ]
4-(4-methyl-3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)phenylcarbamoyl)phenyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87.7%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 12h;	General Procedure for the Preparation of Compounds a1-26 General procedure: To a solution of 4 (4.5 mmol) and 1.5 mL of N,Ndiisopropylethylamine in 30 mL of CH2Cl2 was added 3 (5.4mmol) at 0 - 5 °C, and the reaction mixture was stirred for 12h at room temperature, the solid that formed was collected by filtration. The product was obtained and purified by silica gel chromatography to afford the target product.

Reference： [1]Yao, Ri-Sheng; Guan, Qiu-Xiang; Lu, Xiao-Qin; Ruan, Ban-Feng [Letters in drug design and discovery, 2015, vol. 12, # 1, p. 20 - 28]

40
[ 27914-73-4 ]
[ 57-68-1 ]
4-((4-(N-(4,6-dimethylpyrimidin-2-yl)sulfamoyl)phenyl)carbamoyl)phenyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With pyridine In tetrahydrofuran at 1.84 - 20℃; for 25.5h;
62%	With pyridine In acetone at 0 - 20℃; for 20h;
	With pyridine In acetone at 0 - 20℃; for 20h;	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.

Reference： [1]Zhang, Xuehong; Lin, Yijie; Liu, Lina; Lin, Cuiwu [Luminescence, 2015, vol. 30, # 3, p. 269 - 279]
[2]Gokcen, Taner; Gulcin, Ilhami; Ozturk, Turan; Goren, Ahmet C. [Journal of Enzyme Inhibition and Medicinal Chemistry, 2016, vol. 31, p. 180 - 188]
[3]Köksal, Zeynep; Kalin, Ramazan; Camadan, Yasemin; Usanmaz, Hande; Almaz, Züleyha; Gülçin, Ilhami; Gokcen, Taner; Gören, Ahmet Ceyhan; Ozdemir, Hasan [Molecules, 2017, vol. 22, # 6]

41
[ 27914-73-4 ]
[ 865798-13-6 ]
4-[(4-((trimethylsilyl)ethyn-2-yl)pyridin-2-yl)carbamoyl]phenyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With pyridine In dichloromethane at 20℃;	6 Preparation of 4- [(4-((trimethylsilyl)ethyn-2-yl)pyridin-2-yl)carbamoyl]phenyl acetate A solution of 4-acetoxybenzoyl chloride (1.3 g, 6.67 mmol 1.0 eq.) in dichloromethane (8 mL) was added slowly to a solution of 4-((trimethylsilyl)ethyn-2-yl)pyridin-2-amine (1.27 g, 6.67 mmol) in pyridine (10 mL) and the brown solution was stirred overnight at RT. The reaction mixture was poured into water and extracted two times with dichloromethane. The combined organic extracts were washed with brine, dried over Na2SO4 and concentrated in vacuo. The brown oil was taken up in toluene and concentrated in vacuo. The residue was purified by Si02- chromatography (0 to 40% ethyl acetate in heptane) to give the title compound (1.32 g, 56%) as a yellow solid.

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/55982, 2016, A1 Location in patent: Paragraph 00178

42
[ 27914-73-4 ]
[ 944401-77-8 ]
4-[(4-fluoropyridin-2-yl)carbamoyl]phenyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	In pyridine; dichloromethane at 20℃;	7 Preparation of 4-[(4-fluoropyridin-2-yl)carbamoyl]phenyl acetate A solution of 4- acetoxybenzoyl chloride (1.77 g, 8.92 mmol 1.0 eq.) in dichloromethane (8 mL) was added slowly to a solution of 2-amino-4-fluoropyridine (1.0 g, 8.92 mmol) in pyridine (10 mL) and the brown solution was stirred overnight at RT. The reaction mixture was concentrated to a small volume (to remove DCM), poured into water. The solids were filtered off, washed with water and taken up in toluene and concentrated in vacuo to yield the title compound (2.38 g, 97%) as an off white solid. LC-MS (Method A) Rt: 6.83 mm; m/z 275.1 (M+H)+

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - WO2016/55982, 2016, A1 Location in patent: Paragraph 00180

43
[ 27914-73-4 ]
3-amino-7-chloro-1-methyl-1,6-naphthyridin-2(1H)-one [ No CAS ]
N-(7-chloro-1-methyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-4-hydroxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	Stage #1: 4-acetoxybenzoyl chloride; 3-amino-7-chloro-1-methyl-1,6-naphthyridin-2(1H)-one With pyridine for 5h; Reflux; Stage #2: With sodium hydroxide In methanol; water at 20℃; for 2h;	4.1.2.5 N-(7-Chloro-1-methyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-4-hydroxybenzamide (11) The reaction was carried out using amine 6 (400mg, 1.91mmol) and 4-(acetyloxy)benzoyl chloride [32] (1.25g, 6.30mmol) and refluxed in pyridine for 5h. After concentration under reduced pressure, NaOH (108mg, 2.69mmol, 1.4equiv.) was added to a stirred solution of the crude product in MeOH/ water 1:1 (30mL). After 2hat room temperature, the reaction mixture was acidified to pH 5 with concentrated HCl. The precipitate was collected by filtration and rinsed with cold EtOH to afford 11 (394mg, 63% yield, 2 steps) as a yellow powder. Mp: 325-326°C; IR, ν (cm-1): 3264 (νN-H, νO-H); 1628, 1574 (νC=O); 1504 (νC=C); 756 (νC-Cl); 1H NMR (400MHz, DMSO-d6) δ 10.35 (s, 1H, OH), 9.41 (s, 1H, NH), 8.85 (s, 1H, H5), 8.81 (s, 1H, H4), 7.87 (d, 3J=8.5Hz, 2H, Hb), 7.71 (s, 1H, H8), 6.96 (d, 3J=8.5Hz, 2H, Hc), 3.76 (s, 3H, NCH3); 13C NMR (100MHz, DMSO-d6) δ 164.77 (NH-C=O), 161.33 (Cd), 157.71 (C3-C=O), 149.43 (C5), 148.67 (C8a), 142.34 (C7), 129.38 (2Cb), 128.74 (C3), 123.90 (Ca), 116.74 (C4), 116.04 (C4a), 115.48 (2Cc), 108.67 (C8), 30.26 (NCH3); MS (ESI) m/z (%): 330.1 (100) [M+H]+, 332.1 (40) [M+H+2]+; UPLC purity=98%, Rt 2.52min; HRMS (ESI): calcd. for C16H12ClN3O3 [M+H]+ 330.0640, found: 330.0635.

Reference： [1]Montoir, David; Barillé-Nion, Sophie; Tonnerre, Alain; Juin, Philippe; Duflos, Muriel; Bazin, Marc-Antoine [European Journal of Medicinal Chemistry, 2016, vol. 119, p. 17 - 33]

44
[ 27914-73-4 ]
[ 129188-99-4 ]
(3,3,5-trimethylcyclohexane-1,1-diyl)bis(1,4-phenylene)bis(4-acetoxybenzoate) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With pyridine at 110℃;	1.2 (2) Preparation of (3,3,5-trimethylcyclohexane-1,1-diyl)bis(4,1-phenylene)bis(4-acetoxybenzoate) The commercial BPTMC 54g, 1 equiv. Available as diluted by stirring at room temperature, 159g of pyridine, 10 eq. After that Prior Synthesis of 4-acetoxy-benzoyl chloride 88.1g, 3 ~ 4 hours with stirring under reflux at 110 by the addition of 2.2 equivalent to slowly Respectively. Through the thin plate chromatography (TLC) the reaction was terminated by the addition of water after confirming the BPTMC are lost. Made to room temperature, ethyl acetate and 1N hydrochloric acid, and then extracted using distilled water, the organic layer over magnesium sulfate fractionation Removing the residual water remains in the organic layer, the organic layer was filtered to obtain the moisture removed. The organic layer obtained times Using the former evaporator under reduced pressure to remove the solvent. The solvent is removed substance was recrystallized using ethyl acetate and methanol, Of white solid of (3,3,5-trimethyl-cyclohexane-1,1-diyl) bis (4,1- phenylene) bis (4-acetoxy-benzoate).

Reference： [1]Current Patent Assignee: LG CHEM CO.,LTD. - KR2016/10939, 2016, A Location in patent: Paragraph 0091; 0095; 0096

45
[ 27914-73-4 ]
[ 144-83-2 ]
N-(sulfapyridine)-p-acetoxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%	With pyridine In acetone at 0 - 20℃; for 20h;
	With pyridine In acetone at 0 - 20℃; for 20h;	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.

Reference： [1]Gokcen, Taner; Gulcin, Ilhami; Ozturk, Turan; Goren, Ahmet C. [Journal of Enzyme Inhibition and Medicinal Chemistry, 2016, vol. 31, p. 180 - 188]
[2]Köksal, Zeynep; Kalin, Ramazan; Camadan, Yasemin; Usanmaz, Hande; Almaz, Züleyha; Gülçin, Ilhami; Gokcen, Taner; Gören, Ahmet Ceyhan; Ozdemir, Hasan [Molecules, 2017, vol. 22, # 6]

46
[ 27914-73-4 ]
[ 144-82-1 ]
N-(sulfamethizole)-p-acetoxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; In acetone; at 0 - 20℃; for 20h;	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.

Reference： [1]Journal of Enzyme Inhibition and Medicinal Chemistry,2016,vol. 31,p. 180 - 188
[2]Molecules,2017,vol. 22

47
[ 27914-73-4 ]
[ 127-79-7 ]
[ 102077-10-1 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; In acetone; at 0 - 20℃; for 20h;	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.

Reference： [1]Journal of Enzyme Inhibition and Medicinal Chemistry,2016,vol. 31,p. 180 - 188
[2]Molecules,2017,vol. 22

48
[ 27914-73-4 ]
[ 63-74-1 ]
N-(sulfanilamide)-p-acetoxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	With pyridine In acetone at 0 - 20℃; for 20h;
	With pyridine In acetone at 0 - 20℃; for 20h;	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 pyridine In acetone at 0 - 20℃; for 5.5h;

Reference： [1]Gokcen, Taner; Gulcin, Ilhami; Ozturk, Turan; Goren, Ahmet C. [Journal of Enzyme Inhibition and Medicinal Chemistry, 2016, vol. 31, p. 180 - 188]
[2]Köksal, Zeynep; Kalin, Ramazan; Camadan, Yasemin; Usanmaz, Hande; Almaz, Züleyha; Gülçin, Ilhami; Gokcen, Taner; Gören, Ahmet Ceyhan; Ozdemir, Hasan [Molecules, 2017, vol. 22, # 6]
[3]Chen, Cheng; Gao, Han; Liu, Ya; Sun, Le-Yun; Yang, Ke-Wu; Zhen, Jian-Bin [2020, vol. 11, # 2, p. 259 - 267]

49
[ 27914-73-4 ]
[ 127-69-5 ]
N-(sulfisoxazole)-p-acetoxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	With pyridine In acetone at 0 - 20℃; for 20h;
	With pyridine In acetone at 0 - 20℃; for 20h;	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.

Reference： [1]Gokcen, Taner; Gulcin, Ilhami; Ozturk, Turan; Goren, Ahmet C. [Journal of Enzyme Inhibition and Medicinal Chemistry, 2016, vol. 31, p. 180 - 188]
[2]Köksal, Zeynep; Kalin, Ramazan; Camadan, Yasemin; Usanmaz, Hande; Almaz, Züleyha; Gülçin, Ilhami; Gokcen, Taner; Gören, Ahmet Ceyhan; Ozdemir, Hasan [Molecules, 2017, vol. 22, # 6]

50
[ 27914-73-4 ]
[ 72-14-0 ]
N-(sulfathiazole)-p-acetoxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; In acetone; at 0 - 20℃; for 20h;	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.

Reference： [1]Journal of Enzyme Inhibition and Medicinal Chemistry,2016,vol. 31,p. 180 - 188
[2]Molecules,2017,vol. 22

51
[ 27914-73-4 ]
[ 68-35-9 ]
N-(sulfadiazine)-p-acetoxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; In acetone; at 0 - 20℃; for 20h;	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.

Reference： [1]Journal of Enzyme Inhibition and Medicinal Chemistry,2016,vol. 31,p. 180 - 188
[2]Molecules,2017,vol. 22

52
[ 27914-73-4 ]
[ 843-55-0 ]
4-(1-{4-[(4-acetoxybenzoyl)oxy]phenyl}cyclohexyl)phenyl-4-acetoxybenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With pyridine; at 110℃;Reflux;	54 g of commercially available BPZ (Bisphenol Z), 1 equivalent of 159 g of pyridine was diluted with 10 equivalents of stirring at room temperature All. Thereafter, 80.09 g of the synthesized 4-acetoxybenzoyl chloride, 2 equivalents, was added slowly, and the mixture was stirred at 110 C for 3 to 4 hours And the mixture was refluxed and stirred. After confirming the disappearance of BPZ through thin plate chromatography (TLC), water was added to terminate the reaction . The mixture was extracted with ethyl acetate, 1N hydrochloric acid and distilled water to separate the organic layer, and then magnesium sulfate The remaining water remaining in the organic layer was removed and filtered to obtain an organic layer from which moisture was removed. The obtained organic The layer was stripped of solvent using rotary evaporator. The solvent-removed material was purified by using ethyl acetate and methanol To give 4- (1- {4 - [(4-acetoxybenzoyl) oxy] phenyl} cyclohexyl) phenyl 4-acetoxybenzoate as a white solid 106.77 g, and 89% yield. The obtained 4- (1- {4 - [(4-acetoxybenzoyl) oxy] phenyl} cyclohexyl) phenyl 4-acetoxybenzene The crude was identified by & lt; 1 & gt; H NMR
89%	With pyridine; at 110℃;	54 g of commercially available BPZ (Bisphenol Z), 1 equivalent of 159 g of pyridine was diluted with 10 equivalents of stirring at room temperature.Thereafter, 88.1 g of the synthesized 4-acetoxybenzoyl chloride, 2.2 equivalents, was added slowly and the mixture was refluxed and stirred at 110 for 3 to 4 hours.After confirming the disappearance of BPZ through thin plate chromatography (TLC), water was added to terminate the reaction.After the organic layer was separated by extraction with ethyl acetate, 1N hydrochloric acid and distilled water, residual water remaining in the organic layer was removed through magnesium sulfate,This was filtered to obtain an organic layer from which moisture was removed. The solvent was removed from the obtained organic layer using a rotary evaporator.The solvent-removed material was recrystallized from ethyl acetate and methanol to give whiteTo obtain 106.77 g of a solid 4- (1- {4 - [(4-acetoxybenzoyl) oxy] phenyl} cyclohexyl) phenyl 4-acetoxybenzoate in 89% yield,The prepared 4- (1- {4 - [(4-acetoxybenzoyl) oxy] phenyl} cyclohexyl) phenyl 4-acetoxybenzoate was confirmed by 1H NMR.

Reference： [1]Patent: KR2016/4501,2016,A .Location in patent: Paragraph 0088;0089
[2]Patent: KR2016/26062,2016,A .Location in patent: Paragraph 0072; 0076; 0077

53
[ 27914-73-4 ]
[ 2026-70-2 ]
C₁₇H₁₄F₃NO₃ [ No CAS ]

Reference： [1]Advanced Synthesis and Catalysis,2017,vol. 359,p. 4393 - 4398

54
[ 27914-73-4 ]
[ 79-19-6 ]
[ 7001-76-5 ]

Yield	Reaction Conditions	Operation in experiment
89%	In tetrahydrofuran at 20℃; for 24h;	R.1 3.1.1. Synthesis of 4-(2-thiocarbamoylhydrazinocarbonyl) phenyl acetate(2) 3.1.1 Synthesis of 4-(2-thiocarbamoylhydrazinocarbonyl) phenyl acetate (2) 4-Acetoxy benzoyl chloride (11 g, 55 mmol) was dissolved in dry THF (70 mL) and the obtained solution was poured to a stirred suspension of thiosemicarbazide (10 g, 109.8 mmol, 2 equv) in dry THF (240 mL). The reaction mixture was stirred at room temperature for 24 h. The THF was evaporated, distilled water (50 mL) was added to the dry solid and vigorously stirred for 5 min. The product was filtered to give white solid. The product was used in the next step without further purification as white solid; Yield 89%; mp 205-207 °C; IR (cm-1, KBr): 3353, 3296 (NH2, NH), 1749 (C=O ester) 1623 (C=O amidic); 1H NMR (90 MHz, δ ppm DMSO-d6): 2.3 (s, 3H, CH3), 7.15,7.9 (dd, J = 9 Hz, 4H, Ar-H), 7.65 (br. s, 2H, NH2), 9.3 (br. s, 1H, NH), 10.3 (br. s, 1H, NH); Elemental analysis for C10H11N3O3S (253.28): Calculated/Found: 47.42/47.69 (%C), 4.38/4.61 (%H), 16.59/16.75 (%N) and 12.66/12.49 (%S).

Reference： [1]Omar, Yasser M.; Abdu-Allah, Hajjaj H.M.; Abdel-Moty, Samia G. [Bioorganic Chemistry, 2018, vol. 80, p. 461 - 471]

55
[ 27914-73-4 ]
[ 19840-99-4 ]
7-N-(4-acetoxybenzoyl)amino-4-methylquinolin-2(1H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With triethylamine; In dichloromethane; for 0.25h;	General procedure: <strong>[19840-99-4]7-amino-4-methylquinolin-2(1H)-one</strong> (1.00 eq) was dissolved in dichloromethane and stirred for 15 min at ambient temperature, meanwhile, the triethylamine (1.05 eq) was added. After 15 min the proper benzoyl chloride (1.05 eq) was added dropwise (benzoyl chloride for compound 2; 3-acetoxy-benzoyl chloride for compound 3; 4-acetoxybenzoylchloride for compound 4; 3,4-diacetoxybenzoyl chloride for compound 5; 3,5-diacetoxybenzoyl chloridefor compound 6; 3,4,5-triacetoxybenzoyl chloride for compound 7). The course of the reaction was monitored by TLC. After 15 min product was filtrated and recrystallized from CH2Cl2: (CH3)2CO 1 : 1

Reference： [1]Acta poloniae pharmaceutica,2018,vol. 75,p. 903 - 910

56
[ 27914-73-4 ]
[ 4774-24-7 ]
2-(4-(4-acetoxybenzoyl)-1-piperazinyl)-quinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: 2-(piperazin-1-yl)quinoline With triethylamine In dichloromethane at 20℃; for 0.25h; Stage #2: 4-acetoxybenzoyl chloride In dichloromethane at 20℃; for 0.25h;	Procedure for the preparation of compounds 9-13 (step V in Scheme 2) Quipazine 4 (1.00 eq) was dissolved in dichloromethane and stirred for 15 min at ambient temperature, meanwhile, the triethylamine (1.05 eq) was added. After 15 min the appropriate benzoyl chloride dissolved in dichloromethane (1.05 eq) was added dropwise (benzoyl chloride for compound 9, 3-acetoxybenzoyl chloride for compound 10, 4-acetoxybenzoyl chloride for compound 11, 3, 4-diacetoxybenzoyl chloride for compound 12, 3,4,5-triacetoxybenzoyl chloride for compound 13. Chlorides were obtained according to the well-known method heating with thionyl chloride at 80°C for one hour). The course of reaction was monitored by TLC (C6H14 : (CH3)2CO 2 : 1). After 15 min water was added and the mixture was extracted by CH2Cl2 (3 X 20 mL). Then, the solvent was evaporated and the remaining product was purified by column chromatography on silica gel (eluent CH2Cl2 : (CH3)2CO99 : 1).

Reference： [1]Kubica, Krzysztof P.; Taciak, Przemysław P.; Czajkowska, Agnieszka; Stokfisz-Ignasiak, Alicja; Wyrebiak, Rafał; Podsadni, Piotr; Młynarczuk-Biały, Izabela; Malejczyk, Jacek; Mazurek, Aleksander P. [Acta poloniae pharmaceutica, 2018, vol. 75, # 4, p. 891 - 901]

57
[ 27914-73-4 ]
[ 50693-78-2 ]
4-methyl-2-(4-(4-acetoxybenzoyl)-1-piperazinyl)-quinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	Stage #1: 4-methyl-2-(piperazin-1-yl)quinoline With triethylamine In dichloromethane at 20℃; for 0.25h; Stage #2: 4-acetoxybenzoyl chloride In dichloromethane at 20℃; for 0.25h;	Procedure for the preparation of compounds 19-23 (Step V in Scheme 3) 4-Methyl-2-(piperazin-1-yl)quinoline 8 (1.00 eq) was dissolved in dichloromethane and stirred for 15 min at ambient temperature, meanwhile, the triethylamine (1.05 eq) was added. After 15 min corresponding benzoyl chloride dissolved in dichloromethane (1.05 eq) was added dropwise (benzoyl chloride for compound 19, 3-acetoxybenzoyl chloride for compound 20, 4-acetoxybenzoyl chloride for compound 21, 3,4-diacetoxybenzoyl chloride for compound 22, 3,4,5-triacetoxybenzoyl chloride for compound 23. Chlorides were obtained according to the well-known method heating with thionyl chloride at 80°C for one hour). The course of the reaction was monitored by TLC (C6H14 : (CH3)2CO 2 : 1). After 15 min water was added and the mixture was extracted by CH2Cl2 (3X 20 mL). Then, the solvent was evaporated and the remaining product was purified by column chromatography on silica gel (eluent CH2Cl2 :(CH3)2CO 99 : 1).

Reference： [1]Kubica, Krzysztof P.; Taciak, Przemysław P.; Czajkowska, Agnieszka; Stokfisz-Ignasiak, Alicja; Wyrebiak, Rafał; Podsadni, Piotr; Młynarczuk-Biały, Izabela; Malejczyk, Jacek; Mazurek, Aleksander P. [Acta poloniae pharmaceutica, 2018, vol. 75, # 4, p. 891 - 901]

58
[ 27914-73-4 ]
[ 33332-29-5 ]
4-((5-chloropyrazin-2-yl)carbamoyl)phenyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%		General procedure: Method B is a modification of Method A and was performed under nitrogen atmosphere andwith extended work-up. Substituted benzoyl chloride (1.5 mmol, 1.2 equiv) was placed into the askunder nitrogen, diluted with dry DCM (5 mL) and dry pyridine (400 mg, 5 mmol, 4 equiv) was added.The mixture was mixed for 5 min under nitrogen. Then, <strong>[33332-29-5]5-chloropyrazin-2-amine</strong> (162 mg, 1.25 mmol,1 equiv) dissolved in DCM (10 mL) was added dropwise over 10 min under nitrogen ow. The askwas closed by septum and stirred for additional 6 h. After reaction, the mixture was diluted with DCMto the final volume of 40 mL and washed with water (1 30 mL), 5% (m/m) aqueous NaHCO3 solution(1 30 mL), and brine (1 30 mL). The organic layer was dried over anhydrous Na2SO4 and adsorbedon silica (4 g) by evaporating the solvents under reduced pressure. Automated flash chromatographywas run using same conditions as described in Method A. If needed, the products were recrystallizedfrom hot EtOH (crystallization initiated by cooling and dropwise addition of cold water).

Reference： [1]Molecules,2018,vol. 23

59
[ 27914-73-4 ]
[ 66-22-8 ]
1-(4-acetoxybenzoyl)-(1H,3H)-pyrimidine-2,4-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With pyridine In chloroform at 20℃; for 1h;	General procedure for the synthesis of 1,3-bis(RObenzoyl)-(1H,3H)-pyrimidine-2,4-diones (I), (III),(VI), (VII), (IX), (X) derivatives ), (XI), (XII), (XIV) General procedure: A solution of 200 mmol of RO-benzoyl chloridein 10 mL of chloroform was added dropwise over15 min to a solution of 100 mmol of uracil or thymine in 30 mL of dry pyridine. A solid product and pyridine hydrochloride were precipitated. The mixture was stirred for 1 h at room temperature. Then the solution was filtered under vacuum; the precipitate was washed with cold water and recrystallized from benzene. N1-Derivatives of uracil and thymine (II), (IV),(V), (VIII), (XIII) were obtained similarly at a molar ratio of starting materials of 1 : 1.

Reference： [1]Spasov; Brel; Litvinov; Lisina; Kucheryavenko; Budaeva, Yu. N.; Salaznikova; Rashchenko; Shamshina; Batrakov; Ivanov [Russian Journal of Bioorganic Chemistry, 2018, vol. 44, # 6, p. 769 - 777][Bioorg. Khim., 2018, vol. 44, # 6, p. 769 - 777,9]

60
[ 27914-73-4 ]
[ 65-71-4 ]
1,3-bis(4-acetoxybenzoyl)-5-methyl-(1H,3H)-pyrimidine-2,4-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With pyridine In chloroform at 20℃; for 1h;	General procedure for the synthesis of 1,3-bis(RObenzoyl)-(1H,3H)-pyrimidine-2,4-diones (I), (III),(VI), (VII), (IX), (X) derivatives ), (XI), (XII), (XIV) General procedure: A solution of 200 mmol of RO-benzoyl chloridein 10 mL of chloroform was added dropwise over15 min to a solution of 100 mmol of uracil or thymine in 30 mL of dry pyridine. A solid product and pyridine hydrochloride were precipitated. The mixture was stirred for 1 h at room temperature. Then the solution was filtered under vacuum; the precipitate was washed with cold water and recrystallized from benzene. N1-Derivatives of uracil and thymine (II), (IV),(V), (VIII), (XIII) were obtained similarly at a molar ratio of starting materials of 1 : 1.

Reference： [1]Spasov; Brel; Litvinov; Lisina; Kucheryavenko; Budaeva, Yu. N.; Salaznikova; Rashchenko; Shamshina; Batrakov; Ivanov [Russian Journal of Bioorganic Chemistry, 2018, vol. 44, # 6, p. 769 - 777][Bioorg. Khim., 2018, vol. 44, # 6, p. 769 - 777,9]

61
[ 27914-73-4 ]
[ 56762-32-4 ]
[4-[(2-acetyl-6-chlorophenyl)carbamoyl]phenyl]acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
37.4%	With triethylamine; In dichloromethane; at 0 - 50℃;	To a solution of l-(2-amino-3-chloro-phenyl)ethanone (3.0 g, 17.7 mmol) and TEA (3.4 g, 34.0 mmol) in DCM (20 mL) cooled at 0 C was added the solution of (4-chlorocarbonylphenyl) acetate (3.4 g, 17.7 mg) in DCM (20 mL) dropwise. After addition, the mixture was stirred at 50 C overnight. After the reaction was completed, the mixture was concentrated in vacuo. The residue was purified by preparative HPLC to give [4-[(2-acetyl-6-chloro- phenyl)carbamoyl]phenyl] acetate (2.2 g, 37.4% yield) as a white solid. MS obsd. (ESI+) [(M+H)+]: 332.1.

Reference： [1]Patent: WO2019/121357,2019,A1 .Location in patent: Page/Page column 37-38

62
[ 27914-73-4 ]
[ 328975-04-8 ]
methyl N-(4-acetoxybenzoyl)-S-allyl-L-cysteinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: (2R)-3-allylsulfanyl-2-amino-propionic acid methyl ester With triethylamine In dichloromethane for 0.5h; Stage #2: 4-acetoxybenzoyl chloride In dichloromethane at 0℃; for 12h;	5.1.5. General procedure for the synthesis of compounds 8a-f, 9a-r General procedure: To a solution of methyl (S)-2-aminopent-4-enoate 2a (600 mg,4.648 mmol) in CH2Cl2 (4 mL) was added triethylamine (1500 mg,14.823 mmol). The mixture was allowed to stir 30 min. 3,4,5-trimethoxybenzoyl chloride 7a (1069 mg, 4.648 mmol) in CH2Cl2(2 mL) was added dropwise at 0 °C. The reaction mixture was stirredfor 12 h. The reaction was then concentrated and the residuewas purified on a silica gel column eluting with 50% ethyl acetate inpetroleum. Yielding 76% compound 8a (1141 mg) as a white solid.Compounds 8b-c and 9a-r were synthesized following the procedureof preparation 8a.

Reference： [1]Bi, Jingjie; Wang, Wenqing; Du, Junxi; Chen, Kun; Cheng, Kui [European Journal of Medicinal Chemistry, 2019, vol. 179, p. 233 - 245]

63
[ 27914-73-4 ]
C₈H₁₅NO₂S [ No CAS ]
methyl N-(4-acetoxybenzoyl)-S-(but-3-en-1-yl)-L-cysteinate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	Stage #1: C₈H₁₅NO₂S With triethylamine In dichloromethane for 0.5h; Stage #2: 4-acetoxybenzoyl chloride In dichloromethane at 0℃; for 12h;	5.1.5. General procedure for the synthesis of compounds 8a-f, 9a-r General procedure: To a solution of methyl (S)-2-aminopent-4-enoate 2a (600 mg,4.648 mmol) in CH2Cl2 (4 mL) was added triethylamine (1500 mg,14.823 mmol). The mixture was allowed to stir 30 min. 3,4,5-trimethoxybenzoyl chloride 7a (1069 mg, 4.648 mmol) in CH2Cl2(2 mL) was added dropwise at 0 °C. The reaction mixture was stirredfor 12 h. The reaction was then concentrated and the residuewas purified on a silica gel column eluting with 50% ethyl acetate inpetroleum. Yielding 76% compound 8a (1141 mg) as a white solid.Compounds 8b-c and 9a-r were synthesized following the procedureof preparation 8a.

Reference： [1]Bi, Jingjie; Wang, Wenqing; Du, Junxi; Chen, Kun; Cheng, Kui [European Journal of Medicinal Chemistry, 2019, vol. 179, p. 233 - 245]

64
[ 27914-73-4 ]
2,3-O-isopropylidene-D-ribofuranose [ No CAS ]
C₁₇H₂₀O₈ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With pyridine at 20℃; for 0.5h;	1.2.1 1. Step 1 P-acetoxybenzoyl chloride (313 mg, 1.6 mmol, 1.2 eq.) was added to the agitated pyridine solution (3 ml) containing riboside 9 (240 mg, 1.33 mmol). The mixture was stirred at room temperature for 30 minutes, then diluted with dichloromethane, washed with 1M HCl and water and saturated with an equal volume of NaHCO3 solution. Thereafter, it was dried and concentrated in vacuo The residue was subjected to silica gel column chromatography on a 1:3 volume ratio of ethyl acetate-toluene. As a result, 421 mg (90%) of a riboside 10 compound was obtained as a mixture of anomers. HMRS-ES positive mode: m/z found 375.1059 [M+Na]+; calcd. for C17H20NaO8 375.1056.

Reference： [1]Current Patent Assignee: INJE UNIVERSITY - US2019/218206, 2019, A1 Location in patent: Paragraph 0066-0072

65
[ 27914-73-4 ]
[ 213192-26-8 ]
methyl 2-(4-acetoxybenzamido)-6-(tert-butyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;	3 Step A. Methyl 6-(tert-butyl)-2-(4-hydroxybenzamido)-4, 5,6,7- tetrahydrobenzo[b]thiophene-3-carboxylate To a solution of methyl 2-amino-6-/er/-butyl-4,5,6,7-tctrahydro- 1 -bcnzothiophcnc-3-carboxylatc (CAS: 213192-26-8, 800 mg, 2.99 mmol) in DCM (70 ml) was added DIPEA (CAS: 7087-68-5, 2.10 ml, 11.97 mmol) and 4-acetoxybenzoyl chloride (CAS: 27914-73-4, 772 mg, 3.89 mmol).The reaction mixture was stirred at RT overnight. The resulting mixture was diluted with DCM. The organic phase was washed with an aqueous 1M HC1 solution and dried over MgS04. The solvent was removed under reduced pressure. The residue was purified by trituration with Et20/isohexane to give methyl 2-(4-acetoxybenzamido)-6-(tert-butyl)-4, 5,6,7- tetrahydrobenzo[b]thiophene-3-carboxylate as white solid (1.20 g, yield 93%). Methyl 2-(4- acetoxybenzamido)-6-(/er/-butyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (430 mg, 1.00 mmol) was suspended in THF (10 ml) and MeOH (10 ml) and LiOH aq. (CAS: 1310-66-3, 1M, 126 mg, 3.0 mmol) was added. The reaction mixture was stirred at RT for 5 minutes and then acidified with 1N aqueous HC1 solution. The precipitate was filtered off and washed with MeOH/FTO to afford methyl 6-(tert-butyl)-2-(4-hydroxybenzamido)-4, 5,6, 7- tetrahydrobenzo[b]thiophene-3-carboxylate as a white solid (330 mg, yield 85%).1H NMR (DMSO-de, 400MHz): d = 11.92 (s, 1H), 10.44 (s, 1H), 7.79 (d, J=8.7 Hz, 2H), 6.96 (d, J=8.7 Hz, 2H), 3.86 (s, 3H), 2.99 (dd, J=l6.5, 3.8 Hz, 1H), 2.69 (dd, J=l6.0, 4.0 Hz, 1H), 2.55 - 2.47 (m, 1H, partially obscured by the DMSO peak), 2.41 - 2.34 (m, 1H), 2.00 - 1.95 (m, 1H), 1.43 (td, J=l 1.4, 3.6 Hz, 1H), 1.22 (qd, J=l2.5, 5.1 Hz, 1H), 0.92 (s, 9H).

Reference： [1]Current Patent Assignee: ENYO PHARMA - WO2019/154949, 2019, A1 Location in patent: Page/Page column 119

66
[ 27914-73-4 ]
[ 119004-72-7 ]
methyl 2-(4-hydroxybenzamido)-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%	Stage #1: 4-acetoxybenzoyl chloride; methyl 2-amino-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; Stage #2: With lithium hydroxide monohydrate In tetrahydrofuran; methanol at 40℃; for 0.5h;	18 Example 18. 2-[(4-Hydroxybenzoyl)amino]-6-phenyl-4,5,6,7-tetrahydrobenzothiophene-3- carboxylic acid (Compound 49) To a solution of methyl 2-amino-6-phenyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (Preparation 4, 1.15 g, 4.00 mmol) in DCM (70 ml) was added DIPEA (CAS: 7087-68-5, 3.50 ml, 20.0 mmol) and 4-acetoxybenzoyl chloride (CAS: 27914-73-4, 953 mg, 4.80 mmol). The reaction mixture was stirred at RT overnight. The reaction was partitioned between DCM and a 0.1M aqueous HC1 solution. The two phases were separated and the organic phase was dried over MgSCL. The solvent was removed under reduced pressure. The residue was suspended in THF (25 ml) and MeOH (25 ml) and LiOH aq. (CAS: 1310-66-3, 0.8M, 336 mg, 8.00 mmol) was added. The reaction was set to stir at RT and next heated at 40 °C for 30 minutes. The reaction was allowed to cool to RT and next acidified to pH ~3 with 1N aqueous HC1 solution. The organic solvents were removed under reduced pressure and the aqueous suspension was filtered to afford methyl 2-(4-hydroxybenzamido)-6-phenyl-4,5,6, 7-tetrahydrobenzo[b] thiophene- 3 -carboxy late as a white solid (1.60 g, yield 98%). Methyl 2-(4-hydroxybenzamido)-6-phenyl-4, 5,6,7- tetrahydrobenzo[b]thiophene-3-carboxylate was finally hydrolysed to give 2-[(4- hydroxybenzoyl)amino]-6-phenyl-4,5,6, 7-tetrahydrobenzothiophene-3-carboxylic acid according to the procedure described in Example 10 (white solid, yield 96%).1H NMR (DMSO-de, 400MHz): d = 13.27 (s, 1H), 12.32 (s, 1H), 10.42 (s, 1H), 7.80 - 7.75 (m, 2H), 7.35 - 7.29 (m, 4H), 7.26 - 7.20 (m, 1H), 6.98 - 6.93 (m, 2H), 3.06 - 2.88 (m, 3H), 2.76 (dd, J=l l.0, 14.2 Hz, 2H), 2.02 (d, J=l l.O Hz, 1H), 1.94 - 1.84 (m, 1H). LC/MS (Table 1, Method A) Rt= 5.07 min; MS ra/z: 394 [M+H]+.

Reference： [1]Current Patent Assignee: ENYO PHARMA - WO2019/154949, 2019, A1 Location in patent: Page/Page column 79; 80

67
[ 27914-73-4 ]
[ 99-57-0 ]
4-(5-nitrobenzooxazol-2-yl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	Stage #1: 4-acetoxybenzoyl chloride; 2-hydroxy-5-nitroaniline With pyridine; 4-butanolide at 20℃; for 12h; Stage #2: With toluene-4-sulfonic acid at 200℃; for 7h; Inert atmosphere; Stage #3: With ammonium hydroxide In N,N-dimethyl-formamide at 20℃; for 5h;	1-1 In the reaction vessel, 3.12 g (15.7 mmol) of the obtained chlorinated product was dissolved in 6 mL of sufficiently dehydrated γ-butyrolactone (GBL), and the solution was sealed with a septum cap to give a solution A.Next, in a separate container, 2.34 g (15.2 mmol) of 2-amino-4-nitrophenol represented by the formula (8) was dissolved in 5 mL of GBL, and 2.5 mL of pyridine was added as a deoxidizing agent. Similarly, the solution was tightly stoppered to prepare a solution B.While cooling Solution A in an ice bath and stirring, Solution B was slowly added dropwise to Solution A with a syringe, and after stirring for several hours, it was stirred at room temperature for 12 hours to perform amidation.2.59 g (15.0 mmol) of p-toluenesulfonic acid was added to this solution as an acid catalyst, and the mixture was refluxed at 200° C. for 7 hours in a nitrogen atmosphere.After completion of the reaction, excess solvent was distilled off and concentrated with an evaporator, and this was dropped into a large amount of water to precipitate.The precipitate was filtered off, washed with water and methanol, and vacuum dried at 120° C. for 12 hours to obtain a black powder (yield 43%).This product was a mixture of a hydrolyzed product of the acetoxy form represented by the formula (9) and the acetoxy form represented by the formula (10).Next, to 1.62 g of this mixture, 3.5 mL of 25% aqueous ammonia and 10 mL of DMF were added, and the mixture was stirred at room temperature for 5 hours to complete hydrolysis.After the reaction, dilute hydrochloric acid was added to this to make it weakly acidic, and a precipitate was deposited and filtered.The filtrate was washed with water and vacuum dried at 120° C. for 12 hours to obtain a pure hydrolyzate represented by the formula (10) (melting point 272° C., yield 82%).

Reference： [1]Current Patent Assignee: NISSAN CHEMICAL CORPORATION; TOHO UNIVERSITY - JP6725787, 2020, B2 Location in patent: Paragraph 0054-0056

68
[ 27914-73-4 ]
[ 52708-32-4 ]
4-((4-(3,5-dimethyl-1H-pyrazol-1-yl)phenyl)carbamoyl)phenyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With triethylamine In dichloromethane at 0 - 20℃; for 1h;	1.3 Step 3: 4-((4-(3,5-dimethyl-1H-pyrazol-1-yl)phenyl)carbamoyl)phenylacetate Put 4-(3,5-di-1H-pyrazol-1-yl)aniline (239 mg, 1.28 mmol) and triethylamine (0.7 mL, 4.007 mmol) in a round-bottom flask, dichloromethane (5 mL) was added and dissolved. Then, the prepared 4-(chlorocarbonyl)phenylacetate was dissolved in dichloromethane and slowly added dropwise at 0 °C. When the reaction is completed after stirring for 1 hour at room temperature, It was washed with an aqueous sodium bicarbonate solution and washed with brine. The organic layer was dried over magnesium sulfate and concentrated. It was solidified using diethyl acid, filtered, and dried to obtain a white target compound (379 mg, 85%).

Reference： [1]Current Patent Assignee: KOREA INSTITUTE OF SCIENCE AND TECHNOLOGY; MEDICINAL BIOCONVERGENCE RESEARCH CENTER - KR2021/89290, 2021, A Location in patent: Paragraph 0220; 0221; 0228-0230

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
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CAS No. :	27914-73-4	MDL No. :	MFCD03424709
Formula :	C₉H₇ClO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	CGEOYYBCLBIBLG-UHFFFAOYSA-N
M.W :	198.60	Pubchem ID :	2756254
Synonyms :

Signal Word:	Danger	Class:	8
Precautionary Statements:	P280-P305+P351+P338-P310	UN#:	3261
Hazard Statements:	H314	Packing Group:	Ⅱ
GHS Pictogram:

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

[ CAS No. 27914-73-4 ]

Quality Control of [ 27914-73-4 ]

Related Doc. of [ 27914-73-4 ]

Product Details of [ 27914-73-4 ]

Safety of [ 27914-73-4 ]

Application In Synthesis of [ 27914-73-4 ]

[ 27914-73-4 ] Synthesis Path-Upstream 1~2

[ 27914-73-4 ] Synthesis Path-Downstream 1~68

Related Functional Groups of
[ 27914-73-4 ]

Aryls

Chlorides

Acyl Chlorides

Esters

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

[ CAS No. 27914-73-4 ]

Quality Control of [ 27914-73-4 ]

Related Doc. of [ 27914-73-4 ]

Product Details of [ 27914-73-4 ]

Safety of [ 27914-73-4 ]

Application In Synthesis of [ 27914-73-4 ]

[ 27914-73-4 ] Synthesis Path-Upstream 1~2

[ 27914-73-4 ] Synthesis Path-Downstream 1~68

Related Functional Groups of [ 27914-73-4 ]

Aryls

Chlorides

Acyl Chlorides

Esters

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 27914-73-4 ]