methyl 3,4,5-trihydroxybenzoate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3,4,5-trihydroxy-benzoic acid methyl ester (50 g, 0.27 mol) and Na2B4O7 (50 g) in water (1000 mL) was added Me2SO4 (120 mL) and aqueous NaOH solution (25%, 200 mL) successively at room temperature. The mixture was stirred at room temperature for 6 h before it was cooled to 0° C. The mixture was acidified to pH ˜2 by adding conc. H2SO4 and then filtered. The filtrate was extracted with EtOAc (500 mL×3). The combined organic layers were dried over anhydrous Na2SO4 and evaporated under reduced pressure to give methyl 3,4-dihydroxy-5-methoxybenzoate (15.3 g 47%), which was used in the next step without further purification. was cooled to 0° C filtered The filtrate was extracted with EtOAc (500 mL×3) The combined organic layers were dried over anhydrous Na2SO4 evaporated under reduced pressure

反応条件: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 303 ml of triethylamine is added over 10 minutes at ambient temperature to an agitated mixture of 200 g of methyl gallate and 2 litres of methylene chloride. After dissolution, the reaction medium is cooled down to 0-5° C. then 130 ml of dichlorodimethylsilane is added over one hour at this temperature, agitation is carried out for a further 30 minutes at this temperature. While maintaining the temperature at 0-5° C., 303.2 ml of triethylamine is added over 25 minutes then 227.6 g of tosyl chloride is added over 15 minutes. Agitation is continued for one hour at 0-5° C., and 200 ml of acetic acid then 500 ml of demineralized water are added over 10 minutes under agitation and while allowing the temperature to rise to 20-22° C., and agitation is continued for 15 minutes at 20° C. The methylene chloride is distilled off at a constant volume (3.3 l) under reduced pressure replacing it with demineralized water, agitation is carried out for 2 hours at 20° C., followed by separation, washing with demineralized water, in order to obtain 523 g (damp weight) of methyl 3,4-dihydroxy-5-[((4-methylphenyl)-sulphonyl]oxy]-benzoate (methyl 3-tosylgallate). The damp product obtained is taken up in 2.17 1 de soda (2N) and 2.17 1 of methylene chloride. Agitation is carried out at 20° C. until dissolution is achieved then 18 g of tetrabutylammonium bromide is added at 20° C. then, over 15 minutes at 20° C., 237 ml of dimethyl sulphate is added. The reaction medium is agitated for 1.5 hours at 20-22° C. 78 ml of triethylamine is added at 20-22° C. and agitation is carried out overnight at 20-22° C., followed by decanting and washing with 400 ml of demineralized water, 20 ml of pure acetic acid is added to the organic phase, followed by agitation for 15 minutes, adding 400 ml of demineralized water then decanting. The combined organic phases are concentrated to dryness, firstly under atmospheric pressure then under reduced pressure at 40 mm Hg and 60° C. outside temperature. Entrainment is carried out with 400 ml of methanol then the dry extract obtained is taken up in 600 ml of methanol, heated under reflux until the product has totally dissolved, followed by cooling down to 0-5° C. and agitation for one hour at this temperature. After separation, washing twice with 200 ml of methanol at 10° C. and drying at 40° C. under reduced pressure, 330.4 g of methyl 3,4-dimethoxy-5-[[(4-methylphenyl)-sulphonyl]oxy]-benzoate is thus collected. The crude product is purified by recrystallization from 330 ml of toluene. After 2 hours of agitation −10° C., separation is carried out, followed by washing twice with 82 ml of toluene, cooling down to −15° C. and drying under reduced pressure at 40° C. in order to obtain 230.3 g of the purified sought product. After dissolution While maintaining the temperature at 0-5° C. Agitation is continued for one hour at 0-5° C. to rise to 20-22° C. agitation is continued for 15 minutes at 20° C The methylene chloride is distilled off at a constant volume (3.3 l) under reduced pressure is carried out for 2 hours at 20° C. followed by separation washing with demineralized water, in order

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In 2.95 l of a 5% aqueous solution of borax was dissolved 36.8 g of methyl 3,4,5-trihydroxybenzoate, and the solution was stirred at room temperature for 5 hours. Then, 110.5 ml of dimethyl sulfate and a solution of sodium hydroxide were dropped into the solution and the reaction mixture was further stirred for 5 hours. After cooling, the mixture was made acidic by concentrated sulfuric acid and extracted with ethyl acetate. The solvent was removed from the extract to obtain 25.5 g of methyl 5-methoxy-3,4-dihydroxybenzoate (the yield was 64.5%). the reaction mixture was further stirred for 5 hours After cooling extracted with ethyl acetate The solvent was removed from the extract

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In 2.95 l of a 5% aqueous solution of borax was dissolved 36.8 g of methyl 3,4,5-trihydroxybenzoate, and the solution was stirred at room temperature for 5 hours. Then, 110.5 ml of dimethyl sulfate and a solution of sodium hydroxide were dropped into the solution and the reaction mixture was further stirred for 5 hours. After cooling, the mixture was made acidic by concentrated sulfuric acid and extracted with ethyl acetate. The solvent was removed from the extract to obtain 25.5 g of methyl 5-methoxy-3,4-dihydroxybenzoate (the yield was 64.5%). the reaction mixture was further stirred for 5 hours After cooling extracted with ethyl acetate The solvent was removed from the extract

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In 2.95 l of a 5% aqueous solution of borax was dissolved 36.8 g of methyl 3,4,5-trihydroxybenzoate, and the solution was stirred at room temperature for 5 hours. Then, 110.5 ml of dimethyl sulfate and a solution of sodium hydroxide were dropped into the solution and the reaction mixture was further stirred for 5 hours. After cooling, the mixture was made acidic by concentrated sulfuric acid and extracted with ethyl acetate. The solvent was removed from the extract to obtain 25.5 g of methyl 5-methoxy-3,4-dihydroxybenzoate (the yield was 64.5%). the reaction mixture was further stirred for 5 hours After cooling extracted with ethyl acetate The solvent was removed from the extract

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture comprising 34 4 g of commercially available methyl gallate, 25.8 g of anhydrous potassium carbonate, 400 ml of DMSO and 50.0 g of diiodomethane was stirred at 40° C. for 24 hours in a nitrogen current. After the reaction, the liquid mixture was poured into water and made acidic by 2N hydrochloric acid, the mixture was extracted with ethyl acetate, and the extract was washed with water. The solvent was removed from the extract and the residue was subjected to flash column chromatography [466 g of 230-400 mesh silica gel, solvent n-hexane/acetone (3/1), pressure: 0.4 kg/cm2, 5th to 9th fractions when fractions of 100 ml were collected] to effect purification and obtain 14.8 g of methyl 3-hydroxy-4,5-(methylenedioxy)benzoate (the yield was 40.4%). After the reaction the mixture was extracted with ethyl acetate the extract was washed with water The solvent was removed from the extract the residue was subjected to flash column chromatography [466 g of 230-400 mesh silica gel, solvent n-hexane/acetone (3/1), pressure: 0.4 kg/cm2, 5th to 9th fractions when fractions of 100 ml were collected] purification

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture comprising 34.4 g of commercially available methyl gallate, 25.8 g of anhydrous potassium carbonate, 400 ml of DMSO and 50.0 g of diiodomethane was stirred at 40° C. for 24 hours in a nitrogen current. After the reaction, the liquid mixture was poured into water and made acidic by 2N hydrochloric acid, the mixture was extracted with ethyl acetate, and the extract was washed with water. The solvent was removed from the extract and the residue was subjected to flash column chromatography [466 g of 230-400 mesh silica gel, solvent n-hexane/acetone (3/1), pressure 0.4 kg/cm2, 5th to 9th fractions when fractions of 100 ml were collected] to effect purification and obtain 14.8 g of methyl 3-hydroxy-4,5-(methylenedioxy)benzoate (the yield was 40.4%). After the reaction the mixture was extracted with ethyl acetate the extract was washed with water The solvent was removed from the extract the residue was subjected to flash column chromatography [466 g of 230-400 mesh silica gel, solvent n-hexane/acetone (3/1), pressure 0.4 kg/cm2, 5th to 9th fractions when fractions of 100 ml were collected] purification

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3,4,5-trihydroxy-benzoic acid methyl ester (50 g, 0.27 mol) and Na2B4O7 (50 g) in water (1000 mL) was added Me2SO4 (120 mL) and aqueous NaOH solution (25%, 200 mL) successively at room temperature. The mixture was stirred at room temperature for 6 h before it was cooled to 0° C. The mixture was acidified to pH˜2 by adding conc. H2SO4 and then filtered. The filtrate was extracted with EtOAc (500 mL×3). The combined organic layers were dried over anhydrous Na2SO4 and evaporated under reduced pressure to give methyl 3,4-dihydroxy-5-methoxybenzoate (15.3 g 47%), which was used in the next step without further purification. was cooled to 0° C filtered The filtrate was extracted with EtOAc (500 mL×3) The combined organic layers were dried over anhydrous Na2SO4 evaporated under reduced pressure

反応条件: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 303 ml of triethylamine is added over 10 minutes at ambient temperature to an agitated mixture of 200 g of methyl gallate and 2 liters of methylene chloride. After dissolution, the reaction medium is cooled down to 0-5° C. then 130 ml of dichlorodimethylsilane is added over one hour at this temperature, agitation is carried out for a further 30 minutes at this temperature. While maintaining the temperature at 0-5° C., 303.2 ml of triethylamine is added over 25 minutes then 227.6 g of tosyl chloride is added over 15 minutes. Agitation is continued for one hour at 0-5° C., and 200 ml of acetic acid then 500 ml of demineralized water are added over 10 minutes under agitation and while allowing the temperature to rise to 20-22° C., and agitation is continued for 15 minutes at 20° C. The methylene chloride is distilled off at a constant volume (3.3 l) under reduced pressure replacing it with demineralized water, agitation is carried out for 2 hours at 20° C., followed by separation, washing with demineralized water, in order to obtain 523 g (damp weight) of methyl 3,4-dihydroxy-5-[[(4-methylphenyl)-sulphonyl]oxy)benzoate (methyl 3-tosylgallate). The damp product obtained is taken up in 2.17 l de soda (2N) and 2.17 l of methylene chloride. Agitation is carried out at 20° C. until dissolution is achieved then 18 g of tetrabutylammonium bromide is added at 20° C. then, over 15 minutes at 20° C., 237 ml of dimethyl sulphate is added. The reaction medium is agitated for 1.5 hours at 20-22° C. 78 ml of triethylamine is added at 20-22° C. and agitation is carried out overnight at 20-22° C., followed by decanting and washing with 400 ml of demineralized water, 20 ml of pure acetic acid is added to the organic phase, followed by agitation for 15 minutes, adding 400 ml of demineralized water then decanting. The combined organic phases are concentrated to dryness, firstly under atmospheric pressure then under reduced pressure at 40 mm Hg and 60° C. outside temperature. Entrainment is carried out with 400 ml of methanol then the dry extract obtained is taken up in 600 ml of methanol, heated under reflux until the product has totally dissolved, followed by cooling down to 0-5° C. and agitation for one hour at this temperature. After separation, washing twice with 200 ml of methanol at −10° C. and drying at 40° C. under reduced pressure, 330.4 g of methyl 3,4-dimethoxy-5-[[(4-methylphenyl)-sulphonyl]oxy]-benzoate is thus collected. The crude product is purified by recrystallization from 330 ml of toluene. After 2 hours of agitation at −10° C., separation is carried out, followed by washing twice with 82 ml of toluene, cooling down to −15° C. and drying under reduced pressure at 40° C. in order to obtain 230.3 g of the purified sought product. After dissolution While maintaining the temperature at 0-5° C. Agitation is continued for one hour at 0-5° C. to rise to 20-22° C. agitation is continued for 15 minutes at 20° C The methylene chloride is distilled off at a constant volume (3.3 l) under reduced pressure is carried out for 2 hours at 20° C. followed by separation washing with demineralized water, in order