甲基 3-(2,6-二氟苯基)丙-2-炔酸甲酯

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of (diazomethyl)trimethylsilane (2.0 M in hexanes, 25 mL, 50 mmol) in tetrahydrofuran (100 mL) at −78° C. was added n-butyllithium (2.5 M in hexanes, 20 mL, 50 mmol) over 5 minutes. After the addition was complete, the reaction mixture temperature was maintained at about −78° C. for 30 minutes and then 2,6-difluorobenzaldehyde (7.1 g, 50 mmol) was added portionwise. The reaction mixture was maintained at −78° C. for an additional 30 minutes and then allowed to warm to room temperature, during which time gas evolution occurred. The reaction mixture was again cooled to −78° C. and n-butyllithium (2.5 M in hexanes, 28 mL, 70 mmol) was added over 5 minutes. After 15 minutes at −78° C., methyl chloroformate (7.8 mL, 100 mmol) was added to the reaction mixture. After 30 minutes, the reaction mixture was allowed to warm to 0° C., and then partitioned between diethyl ether and saturated ammonium chloride solution. The organic phase was separated, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel chromatography (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound (8.0 g). After the addition The reaction mixture was maintained at −78° C. for an additional 30 minutes to warm to room temperature, during which time gas evolution The reaction mixture was again cooled to −78° C. After 30 minutes to warm to 0° C. partitioned between diethyl ether and saturated ammonium chloride solution The organic phase was separated dried over magnesium sulfate filtered concentrated under reduced pressure The resulting material was purified by silica gel chromatography (0 to 100% gradient of ethyl acetate in hexanes as eluant)

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of (diazomethyl)trimethylsilane (2.0 M in hexanes, 25 mL, 50 mmol) in tetrahydrofuran (100 mL) at −78° C. was added n-butyllithium (2.5 M in hexanes, 20 mL, 50 mmol) over 5 minutes. After the addition was complete, the reaction mixture temperature was maintained at about −78° C. for 30 minutes and then 2,6-difluorobenzaldehyde (7.1 g, 50 mmol) was added portionwise. The reaction mixture was maintained at −78° C. for an additional 30 minutes and then allowed to warm to room temperature, during which time gas evolution occurred. The reaction mixture was again cooled to −78° C. and n-butyllithium (2.5 M in hexanes, 28 mL, 70 mmol) was added over 5 minutes. After 15 minutes at −78° C., methyl chloroformate (7.8 mL, 100 mmol) was added to the reaction mixture. After 30 minutes, the reaction mixture was allowed to warm to 0° C., and then partitioned between diethyl ether and saturated ammonium chloride solution. The organic phase was separated, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel chromatography (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound (8.0 g). After the addition The reaction mixture was maintained at −78° C. for an additional 30 minutes to warm to room temperature, during which time gas evolution The reaction mixture was again cooled to −78° C. After 30 minutes to warm to 0° C. partitioned between diethyl ether and saturated ammonium chloride solution The organic phase was separated dried over magnesium sulfate filtered concentrated under reduced pressure The resulting material was purified by silica gel chromatography (0 to 100% gradient of ethyl acetate in hexanes as eluant)

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of (diazomethyl)trimethylsilane (2.0 M in hexanes, 25 mL, 50 mmol) in tetrahydrofuran (100 mL) at −78° C. was added n-butyllithium (2.5 M in hexanes, 20 mL, 50 mmol) over 5 minutes. After the addition was complete, the reaction mixture temperature was maintained at about −78° C. for 30 minutes and then 2,6-difluorobenzaldehyde (7.1 g, 50 mmol) was added portionwise. The reaction mixture was maintained at −78° C. for an additional 30 minutes and then allowed to warm to room temperature, during which time gas evolution occurred. The reaction mixture was again cooled to −78° C. and n-butyllithium (2.5 M in hexanes, 28 mL, 70 mmol) was added over 5 minutes. After 15 minutes at −78° C., methyl chloroformate (7.8 mL, 100 mmol) was added to the reaction mixture. After 30 minutes, the reaction mixture was allowed to warm to 0° C., and then partitioned between diethyl ether and saturated ammonium chloride solution. The organic phase was separated, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel chromatography (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound (8.0 g). After the addition The reaction mixture was maintained at −78° C. for an additional 30 minutes to warm to room temperature, during which time gas evolution The reaction mixture was again cooled to −78° C. After 30 minutes to warm to 0° C. partitioned between diethyl ether and saturated ammonium chloride solution The organic phase was separated dried over magnesium sulfate filtered concentrated under reduced pressure The resulting material was purified by silica gel chromatography (0 to 100% gradient of ethyl acetate in hexanes as eluant)

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of (diazomethyl)trimethylsilane (2.0 M in hexanes, 25 mL, 50 mmol) in tetrahydrofuran (100 mL) at −78° C. was added n-butyllithium (2.5 M in hexanes, 20 mL, 50 mmol) over 5 minutes. After the addition was complete, the reaction mixture temperature was maintained at about −78° C. for 30 minutes and then 2,6-difluorobenzaldehyde (7.1 g, 50 mmol) was added portionwise. The reaction mixture was maintained at −78° C. for an additional 30 minutes and then allowed to warm to room temperature, during which time gas evolution occurred. The reaction mixture was again cooled to −78° C. and n-butyllithium (2.5 M in hexanes, 28 mL, 70 mmol) was added over 5 minutes. After 15 minutes at −78° C., methyl chloroformate (7.8 mL, 100 mmol) was added to the reaction mixture. After 30 minutes, the reaction mixture was allowed to warm to 0° C., and then partitioned between diethyl ether and saturated ammonium chloride solution. The organic phase was separated, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel chromatography (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound (8.0 g). After the addition The reaction mixture was maintained at −78° C. for an additional 30 minutes to warm to room temperature, during which time gas evolution The reaction mixture was again cooled to −78° C. After 30 minutes to warm to 0° C. partitioned between diethyl ether and saturated ammonium chloride solution The organic phase was separated dried over magnesium sulfate filtered concentrated under reduced pressure The resulting material was purified by silica gel chromatography (0 to 100% gradient of ethyl acetate in hexanes as eluant)

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of (diazomethyl)trimethylsilane (2.0 M in hexanes, 25 mL, 50 mmol) in tetrahydrofuran (100 mL) at −78° C. was added n-butyllithium (2.5 M in hexanes, 20 mL, 50 mmol) over 5 minutes. After the addition was complete, the reaction mixture temperature was maintained at about −78° C. for 30 minutes and then 2,6-difluorobenzaldehyde (7.1 g, 50 mmol) was added portionwise. The reaction mixture was maintained at −78° C. for an additional 30 minutes and then allowed to warm to room temperature, during which time gas evolution occurred. The reaction mixture was again cooled to −78° C. and n-butyllithium (2.5 M in hexanes, 28 mL, 70 mmol) was added over 5 minutes. After 15 minutes at −78° C., methyl chloroformate (7.8 mL, 100 mmol) was added to the reaction mixture. After 30 minutes, the reaction mixture was allowed to warm to 0° C., and then partitioned between diethyl ether and saturated ammonium chloride solution. The organic phase was separated, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting material was purified by silica gel chromatography (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound (8.0 g). After the addition The reaction mixture was maintained at −78° C. for an additional 30 minutes to warm to room temperature, during which time gas evolution The reaction mixture was again cooled to −78° C. After 30 minutes to warm to 0° C. partitioned between diethyl ether and saturated ammonium chloride solution The organic phase was separated dried over magnesium sulfate filtered concentrated under reduced pressure The resulting material was purified by silica gel chromatography (0 to 100% gradient of ethyl acetate in hexanes as eluant)