ethyl 2-(4-chlorophenyl)-2,2-difluoroacetate

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Lithium aluminum hydride, 2.4 grams (0.063 mole), is placed in a reaction vessel, and 200 mL of diethyl ether is added dropwise with stirring. To this is added dropwise a solution of 22.8 grams (0.097 mole) of ethyl 4-chlorophenyldifluoroacetate (prepared by methods taught by W. J. Middleton et al., J. Org. Chem., (1980), 45, 2883-2887) in 100 mL of diethyl ether, while maintaining the reaction mixture temperature at about 25° C. Upon completion of addition, the reaction mixture is stirred at ambient temperature for about 36 hours. The reaction is then quenched by the careful dropwise addition of an aqueous solution of 10% sodium hydroxide. The reaction mixture is slowly made acidic with aqueous 2N hydrochloric acid and then is diluted with 200 mL of water. The organic layer is separated, and the aqueous layer is washed with two 300 mL portions of diethyl ether. The organic layer and the diethyl ether washes are combined and washed with one 250 mL portion of an aqueous solution saturated with sodium chloride. The organic layer is dried with magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure, yielding 2,2-difluoro-2-(4-chlorophenyl)ethanol. Upon completion of addition the reaction mixture is stirred at ambient temperature for about 36 hours The reaction is then quenched by the careful dropwise addition of an aqueous solution of 10% sodium hydroxide is diluted with 200 mL of water The organic layer is separated the aqueous layer is washed with two 300 mL portions of diethyl ether washed with one 250 mL portion of an aqueous solution saturated with sodium chloride The organic layer is dried with magnesium sulfate filtered The filtrate is concentrated under reduced pressure

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: Ethyl 4-chlorophenyl-2,2-difluoroacetate (250 mg) and potassium hydroxide (300 mg) were mixed in 27 ml of ethanol and 2.4 ml of water and the reaction mixture was refluxed for four hours. The mixture was then acidified and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous Na2SO4 and the solvent was removed in vacuo to give a product which was dissolved in 410 mg of oxalyl chloride with catalytic amount of N,N-dimethylformamide. The mixture was stirred for two hours and excess oxalyl chloride was removed in vacuo to give 4-chlorophenyl-2,2-difluoroethanoyl chloride which was used as is for the subsequent step. extracted with ethyl acetate The organic layer was washed with water dried over anhydrous Na2SO4 the solvent was removed in vacuo to give a product which excess oxalyl chloride was removed in vacuo

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Lithium aluminum hydride, 2.4 grams (0.063 mole), is placed in a reaction vessel, and 200 mL of diethyl ether is added dropwise with stirring. To this is added dropwise a solution of 22.8 grams (0.097 mole) of ethyl 4-chlorophenyldifluoroacetate (prepared by methods taught by W. J. Middleton et al., J. Org. Chem., (1980), 45, 2883-2887) in 100 mL of diethyl ether, while maintaining the reaction mixture temperature at about 25° C. Upon completion of addition, the reaction mixture is stirred at ambient temperature for about 36 hours. The reaction is then quenched by the careful dropwise addition of an aqueous solution of 10% sodium hydroxide. The reaction mixture is slowly made acidic with aqueous 2N hydrochloric acid and then is diluted with 200 mL of water. The organic layer is separated, and the aqueous layer is washed with two 300 mL portions of diethyl ether. The organic layer and the diethyl ether washes are combined and washed with one 250 mL portion of an aqueous solution saturated with sodium chloride. The organic layer is dried with magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure, yielding 2,2-difluoro-2-(4-chlorophenyl)ethanol. Upon completion of addition the reaction mixture is stirred at ambient temperature for about 36 hours The reaction is then quenched by the careful dropwise addition of an aqueous solution of 10% sodium hydroxide is diluted with 200 mL of water The organic layer is separated the aqueous layer is washed with two 300 mL portions of diethyl ether washed with one 250 mL portion of an aqueous solution saturated with sodium chloride The organic layer is dried with magnesium sulfate filtered The filtrate is concentrated under reduced pressure

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Lithium aluminum hydride, 2.4 grams (0.063 mole), is placed in a reaction vessel, and 200 mL of diethyl ether is added dropwise with stirring. To this is added dropwise a solution of 22.8 grams (0.097 mole) of ethyl 4-chlorophenyldifluoroacetate (prepared by methods taught by W. J. Middleton et al., J. Org. Chem., (1980), 45, 2883-2887) in 100 mL of diethyl ether, while maintaining the reaction mixture temperature at about 25° C. Upon completion of addition, the reaction mixture is stirred at ambient temperature for about 36 hours. The reaction is then quenched by the careful dropwise addition of an aqueous solution of 10% sodium hydroxide. The reaction mixture is slowly made acidic with aqueous 2N hydrochloric acid and then is diluted with 200 mL of water. The organic layer is separated, and the aqueous layer is washed with two 300 mL portions of diethyl ether. The organic layer and the diethyl ether washes are combined and washed with one 250 mL portion of an aqueous solution saturated with sodium chloride. The organic layer is dried with magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure, yielding 2,2-difluoro-2-(4-chlorophenyl)ethanol. Upon completion of addition the reaction mixture is stirred at ambient temperature for about 36 hours The reaction is then quenched by the careful dropwise addition of an aqueous solution of 10% sodium hydroxide is diluted with 200 mL of water The organic layer is separated the aqueous layer is washed with two 300 mL portions of diethyl ether washed with one 250 mL portion of an aqueous solution saturated with sodium chloride The organic layer is dried with magnesium sulfate filtered The filtrate is concentrated under reduced pressure

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Lithium aluminum hydride, 2.4 grams (0.063 mole), is placed in a reaction vessel, and 200 mL of diethyl ether is added dropwise with stirring. To this is added dropwise a solution of 22.8 grams (0.097 mole) of ethyl 4-chlorophenyldifluoroacetate (prepared by methods taught by W. J. Middleton et al., J. Org. Chem., (1980), 45, 2883-2887) in 100 mL of diethyl ether, while maintaining the reaction mixture temperature at about 25° C. Upon completion of addition, the reaction mixture is stirred at ambient temperature for about 36 hours. The reaction is then quenched by the careful dropwise addition of an aqueous solution of 10% sodium hydroxide. The reaction mixture is slowly made acidic with aqueous 2N hydrochloric acid and then is diluted with 200 mL of water. The organic layer is separated, and the aqueous layer is washed with two 300 mL portions of diethyl ether. The organic layer and the diethyl ether washes are combined and washed with one 250 mL portion of an aqueous solution saturated with sodium chloride. The organic layer is dried with magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure, yielding 2,2-difluoro-2-(4-chlorophenyl)ethanol. Upon completion of addition the reaction mixture is stirred at ambient temperature for about 36 hours The reaction is then quenched by the careful dropwise addition of an aqueous solution of 10% sodium hydroxide is diluted with 200 mL of water The organic layer is separated the aqueous layer is washed with two 300 mL portions of diethyl ether washed with one 250 mL portion of an aqueous solution saturated with sodium chloride The organic layer is dried with magnesium sulfate filtered The filtrate is concentrated under reduced pressure

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

実験手順: Ethyl 4-chlorophenyl-2,2-difluoroacetate (250 mg) and potassium hydroxide (300 mg) were mixed in 27 ml of ethanol and 2.4 ml of water and the reaction mixture was refluxed for four hours. The mixture was then acidified and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous Na2SO4 and the solvent was removed in vacuo to give a product which was dissolved in 410 mg of oxalyl chloride with catalytic amount of N,N-dimethylformamide. The mixture was stirred for two hours and excess oxalyl chloride was removed in vacuo to give 4-chlorophenyl-2,2-difluoroethanoyl chloride which was used as is for the subsequent step. extracted with ethyl acetate The organic layer was washed with water dried over anhydrous Na2SO4 the solvent was removed in vacuo to give a product which excess oxalyl chloride was removed in vacuo