1-苄氧基-3-氯-2-丙醇

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 204.0 g of 3-benzyloxy-1-chloro-2-propanol, 660 ml of hexane, 626.3 g of methoxymethyl propionate and 5.79 g of p-toluenesulfonic acid mono-hydrate were placed into a 2-liter 3-neck round bottom flask equipped with a thermometer, mechanical stirrer, nitrogen inlet and an efficient distillation column. The reaction mixture was heated to reflux. The distillate was taken off at about 10:1 to 15:1 reflux ratio keeping the head temperature below 60° C. Samples were taken to monitor the progress of the reaction. The reaction was quenched when the desired level of methyl acetal was reached which is usually less than about 4% methyl acetal. The quench was carried out by rapidly adding a solution of 11.55 g of sodium carbonate in 310 ml of water directly to the hot reaction mixture. The aqueous layer was washed with additional water and/or base to remove any residual propionic acid. The volatiles were removed to leave the crude product as a mobile liquid. Yield: 285.2 g, (97.8%); 92.6% pure. equipped with a thermometer, mechanical stirrer, nitrogen inlet an efficient distillation column The reaction mixture was heated to reflux reflux ratio the head temperature below 60° C the progress of the reaction The reaction was quenched when the desired level of methyl acetal by rapidly adding a solution of 11.55 g of sodium carbonate in 310 ml of water directly to the hot reaction mixture The aqueous layer was washed with additional water and/or base to remove any residual propionic acid The volatiles were removed

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Epichlorohydrin is reacted with benzyl alcohol in the presence of tetrabutylammonium bisulfate in aqueous sodium hydroxide, at room temperature. The product of this reaction, benzyl glycidyl ether, is isolated by conventional means and is then added slowly to a suspension of lithium chloride in tetrahydrofuran and acetic acid, at 40°-70° C., preferably below 60° C. The reaction mixture is allowed to cool to room temperature, and stirred for 2-10 hours, preferably 3-6 hours. The product is isolated by extraction, washed and dried to provide 1-benzyloxy-3-chloro-2-propanol. To this product is then added methoxymethyl propionate, which is prepared by adding propionic anhydride to dimethoxymethane in the presence of an ion exchange resin, e.g., Amberlyst 15, maintaining the temperature between 40°-60° C., preferably between 40°-50° C. during the addition. The reaction mixture is aged and cooled, then filtered, washed and distilled. This product, methoxymethyl propionate, is reacted with 1-benzyloxy-3-chloro-2-propanol in an aprotic solvent, e.g., hexanes, in the presence of p-toluenesulfonic acid hydrate at reflux. Distillation and washing affords the product 1-benzyloxy-3-chloro-2-(propionyloxy)methoxypropane. Finally, to prepare the compounds of Formula (III), 1-benzyloxy-3-chloro-2-(propionyloxy)methoxypropane, is refluxed with an alkali metal alkanoate, e.g., sodium propionate, in an aprotic solvent, e.g., toluene, after which a phase transfer catalyst such as tetrabutylphosphonium chloride is added. The reaction mixture is stirred at 90° C. to reflux temperature for 1-3 days, preferably 2 days, at which time more tetrabutylphosphonium chloride and solvent may be added, if required. The mixture is heated to reflux and the distillate removed, then stirred at 90° C. to reflux temperature for 3-16 hours, preferably 5-10 hours, then cooled to ambient temperature. The mixture is then washed with water and brine, and the organic phase is separated and concentrated to yield 1-benzyloxy-3-propionyloxy-2-(propionyloxy)methoxy propane. In an analogous manner, other glycerol derivatives of Formula (III) may be prepared. is isolated by conventional means The product is isolated by extraction washed dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 204.0 g of 3-benzyloxy-1-chloro-2-propanol, 660 ml of hexane, 626.3 g of methoxymethyl propionate and 5.79 g of p-toluenesulfonic acid mono-hydrate were placed into a 2-liter 3-neck round bottom flask equipped with a thermometer, mechanical stirrer, nitrogen inlet and an efficient distillation column. The reaction mixture was heated to reflux. The distillate was taken off at about 10:1 to 15:1 reflux ratio keeping the head temperature below 60° C. Samples were taken to monitor the progress of the reaction. The reaction was quenched when the desired level of methyl acetal was reached which is usually less than about 4% methyl acetal. The quench was carried out by rapidly adding a solution of 11.55 g of sodium carbonate in 310 ml of water directly to the hot reaction mixture. The aqueous layer was washed with additional water and/or base to remove any residual propionic acid. The volatiles were removed to leave the crude product as a mobile liquid. Yield: 285.2 g, (97.8%); 92.6% pure.. equipped with a thermometer, mechanical stirrer, nitrogen inlet an efficient distillation column The reaction mixture was heated to reflux reflux ratio the head temperature below 60° C the progress of the reaction The reaction was quenched when the desired level of methyl acetal by rapidly adding a solution of 11.55 g of sodium carbonate in 310 ml of water directly to the hot reaction mixture The aqueous layer was washed with additional water and/or base to remove any residual propionic acid The volatiles were removed

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Epichlorohydrin is reacted with benzyl alcohol in the presence of tetrabutylammonium bisulfate in aqueous sodium hydroxide, at room temperature. The product of this reaction, benzyl glycidyl ether, is isolated by conventional means and is then added slowly to a suspension of lithium chloride in tetrahydrofuran and acetic acid, at 40°-70° C., preferably below 60° C. The reaction mixture is allowed to cool to room temperature, and stirred for 2-10 hours, preferably 3-6 hours. The product is isolated by extraction, washed and dried to provide 1-benzyloxy-3-chloro-2-propanol. To this product is then added methoxymethyl propionate, which is prepared by adding propionic anhydride to dimethoxymethane in the presence of an ion exchange resin, e.g., Amberlyst 15, maintaining the temperature between 40°-60° C., preferably between 40°-50° C. during the addition. The reaction mixture is aged and cooled, then filtered, washed and distilled. This product, methoxymethyl propionate, is reacted with 1-benzyloxy-3-chloro-2-propanol in an aprotic solvent, e.g., hexanes, in the presence of p-toluenesulfonic acid hydrate at reflux. Distillation and washing affords the product 1-benzyloxy-3-chloro-2-(propionyloxy)methoxypropane. Finally, to prepare the compounds of Formula (III), 1-benzyloxy-3-chloro-2-(propionyloxy)methoxypropane, is refluxed with an alkali metal alkanoate, e.g., sodium propionate, in an aprotic solvent, e.g., toluene, after which a phase transfer catalyst such as tetrabutylphosphonium chloride is added. The reaction mixture is stirred at 90° C. to reflux temperature for 1-3 days, preferably 2 days, at which time more tetrabutylphosphonium chloride and solvent may be added, if required. The mixture is heated to reflux and the distillate removed, then stirred at 90° C. to reflux temperature for 3-16 hours, preferably 5-10 hours, then cooled to ambient temperature. The mixture is then washed with water and brine, and the organic phase is separated and concentrated to yield 1-benzyloxy-3-propionyloxy-2-(propionyloxy)methoxy propane. In an analogous manner, other glycerol derivatives of Formula (III) may be prepared. is isolated by conventional means The product is isolated by extraction washed dried

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 1-benzyloxy-3-chloro-propan-2-ol (10.0 g, 50.0 mmol) [prepared according to Journal of Organic Chemistry (1990), 55, 4897] in ethyl acetate (125 mL) was added a solution of NaHCO3 (12.6 g, 150 mmol) and NaBr (5.66 g, 55.0 mmol) in water (75 mL). After cooling of the biphasic mixture to 0° C., 2,2,6,6-Tetramethyl-piperidin-1-yl)oxyl (“TEMPO”) (391 mg, 2.50 mmol) was added in one portion followed by dropwise addition of NaOCl (6 wt % in water, 85.4 mL, 75.0 mmol) to the vigorously stirred solution. After completion of the addition, stirring at 0° C. was continued for 30 min. Subsequently, a solution of aqueous Na2SO3 was added until the reaction mixture had completely discolored. Additional solid Na2SO3 was added to saturate the aqueous phase. The mixture was transferred to a separation funnel and the layers were separated. The organic layer was washed with brine (100 mL), dried (Na2SO4), filtered and concentrated under reduced pressure (at 20° C.). The remaining oil was used without further purification. 1H NMR (400 MHz, CDCl3) 4.26 (s, 2H), 4.33 (s, 2H), 4.62 (s, 2H), 7.31-7.45 (m, 5H). 2,2,6,6-Tetramethyl-piperidin-1-yl)oxyl (“TEMPO”) (391 mg, 2.50 mmol) was added in one portion After completion of the addition to saturate the aqueous phase The mixture was transferred to a separation funnel the layers were separated The organic layer was washed with brine (100 mL) dried (Na2SO4) filtered concentrated under reduced pressure (at 20° C.) The remaining oil was used without further purification

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 1-benzyloxy-3-chloro-propan-2-ol (10.0 g, 50.0 mmol) [prepared according to Journal of Organic Chemistry (1990), 55, 4897] in ethyl acetate (125 mL) was added a solution of NaHCO3 (12.6 g, 150 mmol) and NaBr (5.66 g, 55.0 mmol) in water (75 mL). After cooling of the biphasic mixture to 0° C., 2,2,6,6-Tetramethyl-piperidin-1-yl)oxyl (“TEMPO”) (391 mg, 2.50 mmol) was added in one portion followed by dropwise addition of NaOCl (6 wt % in water, 85.4 mL, 75.0 mmol) to the vigorously stirred solution. After completion of the addition, stirring at 0° C. was continued for 30 min. Subsequently, a solution of aqueous Na2SO3 was added until the reaction mixture had completely discolored. Additional solid Na2SO3 was added to saturate the aqueous phase. The mixture was transferred to a separation funnel and the layers were separated. The organic layer was washed with brine (100 mL), dried (Na2SO4), filtered and concentrated under reduced pressure (at 20° C.). The remaining oil was used without further purification. 1H NMR (400 MHz, CDCl3) 4.26 (s, 2H), 4.33 (s, 2H), 4.62 (s, 2H), 7.31-7.45 (m, 5H). 2,2,6,6-Tetramethyl-piperidin-1-yl)oxyl (“TEMPO”) (391 mg, 2.50 mmol) was added in one portion After completion of the addition to saturate the aqueous phase The mixture was transferred to a separation funnel the layers were separated The organic layer was washed with brine (100 mL) dried (Na2SO4) filtered concentrated under reduced pressure (at 20° C.) The remaining oil was used without further purification

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 204.0 g of 3-benzyloxy-1-chloro-2-propanol, 660 ml of hexane, 626.3 g of methoxymethyl propionate and 5.79 g of p-toluenesulfonic acid mono-hydrate were placed into a 2-liter 3-neck round bottom flask equipped with a thermometer, mechanical stirrer, nitrogen inlet and an efficient distillation column. The reaction mixture was heated to reflux. The distillate was taken off at about 10:1 to 15:1 reflux ratio keeping the head temperature below 60° C. Samples were taken to monitor the progress of the reaction. The reaction was quenched when the desired level of methyl acetal was reached which is usually less than about 4% methyl acetal. The quench was carried out by rapidly adding a solution of 11.55 g of sodium carbonate in 310 ml of water directly to the hot reaction mixture. The aqueous layer was washed with additional water and/or base to remove any residual propionic acid. The volatiles were removed to leave the crude product as a mobile liquid. Yield: 285.2 g, (97.8%); 92.6% pure. equipped with a thermometer, mechanical stirrer, nitrogen inlet an efficient distillation column The reaction mixture was heated to reflux reflux ratio the head temperature below 60° C the progress of the reaction The reaction was quenched when the desired level of methyl acetal by rapidly adding a solution of 11.55 g of sodium carbonate in 310 ml of water directly to the hot reaction mixture The aqueous layer was washed with additional water and/or base to remove any residual propionic acid The volatiles were removed

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 204.0 g of 3-benzyloxy-1-chloro-2-propanol, 660 ml of hexane, 626.3 g of methoxymethyl propionate and 5.79 g of p-toluenesulfonic acid mono-hydrate were placed into a 2-liter 3-neck round bottom flask equipped with a thermometer, mechanical stirrer, nitrogen inlet and an efficient distillation column. The reaction mixture was heated to reflux. The distillate was taken off at about 10:1 to 15:1 reflux ratio keeping the head temperature below 60° C. Samples were taken to monitor the progress of the reaction. The reaction was quenched when the desired level of methyl acetal was reached which is usually less than about 4% methyl acetal. The quench was carried out by rapidly adding a solution of 11.55 g of sodium carbonate in 310 ml of water directly to the hot reaction mixture. The aqueous layer was washed with additional water and/or base to remove any residual propionic acid. The volatiles were removed to leave the crude product as a mobile liquid. Yield: 285.2 g, (97.8%); 92.6% pure. equipped with a thermometer, mechanical stirrer, nitrogen inlet an efficient distillation column The reaction mixture was heated to reflux reflux ratio the head temperature below 60° C the progress of the reaction The reaction was quenched when the desired level of methyl acetal by rapidly adding a solution of 11.55 g of sodium carbonate in 310 ml of water directly to the hot reaction mixture The aqueous layer was washed with additional water and/or base to remove any residual propionic acid The volatiles were removed

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Epichlorohydrin is reacted with benzyl alcohol in the presence of tetrabutylammonium bisulfate in aqueous sodium hydroxide, at room temperature. The product of this reaction, benzyl glycidyl ether, is isolated by conventional means and is then added slowly to a suspension of lithium chloride in tetrahydrofuran and acetic acid, at 40°-70° C., preferably below 60° C. The reaction mixture is allowed to cool to room temperature, and stirred for 2-10 hours, preferably 3-6 hours. The product is isolated by extraction, washed and dried to provide 1-benzyloxy-3-chloro-2-propanol. To this product is then added methoxymethyl propionate, which is prepared by adding propionic anhydride to dimethoxymethane in the presence of an ion exchange resin, e.g., Amberlyst 15, maintaining the temperature between 40°-60° C., preferably between 40°-50° C. during the addition. The reaction mixture is aged and cooled, then filtered, washed and distilled. This product, methoxymethyl propionate, is reacted with 1-benzyloxy-3-chloro-2-propanol in an aprotic solvent, e.g., hexanes, in the presence of p-toluenesulfonic acid hydrate at reflux. Distillation and washing affords the product 1-benzyloxy-3-chloro-2-(propionyloxy)methoxypropane. Finally, to prepare the compounds of Formula (III), 1-benzyloxy-3-chloro-2-(propionyloxy)methoxypropane, is refluxed with an alkali metal alkanoate, e.g., sodium propionate, in an aprotic solvent, e.g., toluene, after which a phase transfer catalyst such as tetrabutylphosphonium chloride is added. The reaction mixture is stirred at 90° C. to reflux temperature for 1-3 days, preferably 2 days, at which time more tetrabutylphosphonium chloride and solvent may be added, if required. The mixture is heated to reflux and the distillate removed, then stirred at 90° C. to reflux temperature for 3-16 hours, preferably 5-10 hours, then cooled to ambient temperature. The mixture is then washed with water and brine, and the organic phase is separated and concentrated to yield 1-benzyloxy-3-propionyloxy-2-(propionyloxy)methoxy propane. In an analogous manner, other glycerol derivatives of Formula (III) may be prepared. is isolated by conventional means The product is isolated by extraction washed dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 204.0 g of 3-benzyloxy-1-chloro-2-propanol, 660 ml of hexane, 626.3 g of methoxymethyl propionate and 5.79 g of p-toluenesulfonic acid mono-hydrate were placed into a 2-liter 3-neck round bottom flask equipped with a thermometer, mechanical stirrer, nitrogen inlet and an efficient distillation column. The reaction mixture was heated to reflux. The distillate was taken off at about 10:1 to 15:1 reflux ratio keeping the head temperature below 60° C. Samples were taken to monitor the progress of the reaction. The reaction was quenched when the desired level of methyl acetal was reached which is usually less than about 4% methyl acetal. The quench was carried out by rapidly adding a solution of 11.55 g of sodium carbonate in 310 ml of water directly to the hot reaction mixture. The aqueous layer was washed with additional water and/or base to remove any residual propionic acid. The volatiles were removed to leave the crude product as a mobile liquid. Yield: 285.2 g, (97.8%); 92.6% pure.. equipped with a thermometer, mechanical stirrer, nitrogen inlet an efficient distillation column The reaction mixture was heated to reflux reflux ratio the head temperature below 60° C the progress of the reaction The reaction was quenched when the desired level of methyl acetal by rapidly adding a solution of 11.55 g of sodium carbonate in 310 ml of water directly to the hot reaction mixture The aqueous layer was washed with additional water and/or base to remove any residual propionic acid The volatiles were removed

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 204.0 g of 3-benzyloxy-1-chloro-2-propanol, 660 ml of hexane, 626.3 g of methoxymethyl propionate and 5.79 g of p-toluenesulfonic acid mono-hydrate were placed into a 2-liter 3-neck round bottom flask equipped with a thermometer, mechanical stirrer, nitrogen inlet and an efficient distillation column. The reaction mixture was heated to reflux. The distillate was taken off at about 10:1 to 15:1 reflux ratio keeping the head temperature below 60° C. Samples were taken to monitor the progress of the reaction. The reaction was quenched when the desired level of methyl acetal was reached which is usually less than about 4% methyl acetal. The quench was carried out by rapidly adding a solution of 11.55 g of sodium carbonate in 310 ml of water directly to the hot reaction mixture. The aqueous layer was washed with additional water and/or base to remove any residual propionic acid. The volatiles were removed to leave the crude product as a mobile liquid. Yield: 285.2 g, (97.8%); 92.6% pure.. equipped with a thermometer, mechanical stirrer, nitrogen inlet an efficient distillation column The reaction mixture was heated to reflux reflux ratio the head temperature below 60° C the progress of the reaction The reaction was quenched when the desired level of methyl acetal by rapidly adding a solution of 11.55 g of sodium carbonate in 310 ml of water directly to the hot reaction mixture The aqueous layer was washed with additional water and/or base to remove any residual propionic acid The volatiles were removed