吡咯烷-3-乙酸叔丁酯

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: N-Ethyl-N,N-diisopropylamine (1.80 mL, 10.34 mmol) was added dropwise at room temperature to a solution of 5-bromo-2-chloropyrimidine B-5 (1.00 g, 5.17 mmol) and tert-butyl 2-(pyrrolidin-3-yl)acetate (1.00 g, 5.40 mmol) in anhydrous α,α,α-trifluorotoluene (10.2 mL) under an argon atmosphere, in a 20 mL microwave reactor vial. The reaction mixture was sealed and heated at 120° C. for 30 mins under microwave irradiation, then successively cooled to room temperature, diluted with methylene chloride (100 mL), quenched with a 1 N aqueous solution of hydrogen chloride (30 mL) and decanted. The aqueous layer was extracted with methylene chloride (2×150 mL); the combined extracts were sequentially washed with brine (100 mL), dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure. The crude residue was purified by flash column chromatography on silica gel (hexanes to ethyl acetate gradient) to give tert-butyl 2-(1-(5-bromopyrimidin-2-yl)pyrrolidin-3-yl)acetate B-6 (1.22 g, Yield=69%). MS (ESI), [M+1]+ 342, 344. The reaction mixture was sealed successively cooled to room temperature quenched with a 1 N aqueous solution of hydrogen chloride (30 mL) decanted The aqueous layer was extracted with methylene chloride (2×150 mL) the combined extracts were sequentially washed with brine (100 mL) dried over anhydrous magnesium sulfate filtered concentrated to dryness under reduced pressure The crude residue was purified by flash column chromatography on silica gel (hexanes to ethyl acetate gradient)

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: N-Ethyl-N,N-diisopropylamine (1.80 mL, 10.34 mmol) was added dropwise at room temperature to a solution of 5-bromo-2-chloropyrimidine B-5 (1.00 g, 5.17 mmol) and tert-butyl 2-(pyrrolidin-3-yl)acetate (1.00 g, 5.40 mmol) in anhydrous α,α,α-trifluorotoluene (10.2 mL) under an argon atmosphere, in a 20 mL microwave reactor vial. The reaction mixture was sealed and heated at 120° C. for 30 mins under microwave irradiation, then successively cooled to room temperature, diluted with methylene chloride (100 mL), quenched with a 1 N aqueous solution of hydrogen chloride (30 mL) and decanted. The aqueous layer was extracted with methylene chloride (2×150 mL); the combined extracts were sequentially washed with brine (100 mL), dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure. The crude residue was purified by flash column chromatography on silica gel (hexanes to ethyl acetate gradient) to give tert-butyl 2-(1-(5-bromopyrimidin-2-yl)pyrrolidin-3-yl)acetate B-6 (1.22 g, Yield=69%). MS (ESI), [M+1]+ 342, 344. The reaction mixture was sealed successively cooled to room temperature quenched with a 1 N aqueous solution of hydrogen chloride (30 mL) decanted The aqueous layer was extracted with methylene chloride (2×150 mL) the combined extracts were sequentially washed with brine (100 mL) dried over anhydrous magnesium sulfate filtered concentrated to dryness under reduced pressure The crude residue was purified by flash column chromatography on silica gel (hexanes to ethyl acetate gradient)