tert-butyl (2S)-4-oxo-2-propan-2-ylpyrrolidine-1-carboxylate

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

实验步骤: To a solution of tert-butyl (2S)-4-oxo-2-(propan-2-yl)pyrrolidine-1-carboxylate (500 mg, 2.2 mmol) in THF (10 mL) at −78° C. was added methylmagnesium bromide (1.65 mL, 4.95 mmol) dropwise. The reaction was stirred at −78° C. for 2 hours before warming to room temperature and stirring for an additional 2 hours. The reaction was quenched by slowly adding saturated aqueous ammonium chloride at 0° C. The mixture was acidified with HCl (1N) and extracted with ethyl acetate (2×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography (0-80% ethylacete/hexanes, linear gradient) to afford tert-butyl (2S)-4-hydroxy-4-methyl-2-(propan-2-yl)pyrrolidine-1-carboxylate. before warming to room temperature stirring for an additional 2 hours The reaction was quenched by slowly adding saturated aqueous ammonium chloride at 0° C extracted with ethyl acetate (2×) The combined organic layers were washed with brine dried over sodium sulfate filtered concentrated The residue was purified by silica gel chromatography (0-80% ethylacete/hexanes, linear gradient)

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

实验步骤: Oxalyl chloride (16 mL) dissolved in DCM (200 mL) was placed in a three-neck flask equipped with a stirrer and two addition funnels. One funnel contained DMSO (23 mL) in DCM (100 mL) and the other tert-butyl (2S,4R)-4-hydroxy-2-(propan-2-yl)pyrrolidine-1-carboxylate (37 g) in DCM (100 mL). The contents of the flask were cooled to −78° C., and the DMSO solution was added dropwise. After 15 minutes, tert-butyl (2S,4R)-4-hydroxy-2-(propan-2-yl)pyrrolidine-1-carboxylate was added. The reaction mixture was stirred for 30 minutes, and triethylamine (110 mL) was added. The cooling bath was removed, and water (100 mL) was added at room temperature and stirred for 10 minutes. The organic layer was separated, and the aqueous layer was extracted with DCM (3×100 mL). The combined organic layers were washed with brine (3×50 mL), dried over magnesium sulfate, filtered, and concentrated. The material was purified by silica gel chromatography (petroleum ether/ethyl acetate, 15/1) to afford tert-butyl (2S)-4-oxo-2-(propan-2-yl)pyrrolidine-1-carboxylate. was placed in a three-neck flask equipped with a stirrer two addition funnels The cooling bath was removed water (100 mL) was added at room temperature stirred for 10 minutes The organic layer was separated the aqueous layer was extracted with DCM (3×100 mL) The combined organic layers were washed with brine (3×50 mL) dried over magnesium sulfate filtered concentrated The material was purified by silica gel chromatography (petroleum ether/ethyl acetate, 15/1)

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

实验步骤: To a solution of tert-butyl (2S)-4-oxo-2-(propan-2-yl)pyrrolidine-1-carboxylate (500 mg, 2.2 mmol) in THF (10 mL) at −78° C. was added methylmagnesium bromide (1.65 mL, 4.95 mmol) dropwise. The reaction was stirred at −78° C. for 2 hours before warming to room temperature and stirring for an additional 2 hours. The reaction was quenched by slowly adding saturated aqueous ammonium chloride at 0° C. The mixture was acidified with HCl (1 N) and extracted with ethyl acetate (2×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by silica gel chromatography (0-80% ethylacete/hexanes, linear gradient) to afford tert-butyl (2S)-4-hydroxy-4-methyl-2-(propan-2-yl)pyrrolidine-1-carboxylate. before warming to room temperature stirring for an additional 2 hours The reaction was quenched by slowly adding saturated aqueous ammonium chloride at 0° C extracted with ethyl acetate (2×) The combined organic layers were washed with brine dried over sodium sulfate filtered concentrated The residue was purified by silica gel chromatography (0-80% ethylacete/hexanes, linear gradient)

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

实验步骤: Oxalyl chloride (16 mL) dissolved in DCM (200 mL) was placed in a three-neck flask equipped with a stirrer and two addition funnels. One funnel contained DMSO (23 mL) in DCM (100 mL) and the other tert-butyl (2S,4R)-4-hydroxy-2-(propan-2-yl)pyrrolidine-1-carboxylate (37 g) in DCM (100 mL). The contents of the flask were cooled to −78° C., and the DMSO solution was added dropwise. After 15 minutes, tert-butyl (2S,4R)-4-hydroxy-2-(propan-2-yl)pyrrolidine-1-carboxylate was added. The reaction mixture was stirred for 30 minutes, and triethylamine (110 mL) was added. The cooling bath was removed, and water (100 mL) was added at room temperature and stirred for 10 minutes. The organic layer was separated, and the aqueous layer was extracted with DCM (3×100 mL). The combined organic layers were washed with brine (3×50 mL), dried over magnesium sulfate, filtered, and concentrated. The material was purified by silica gel chromatography (petroleum ether/ethyl acetate, 15/1) to afford tert-butyl (2S)-4-oxo-2-(propan-2-yl)pyrrolidine-1-carboxylate. was placed in a three-neck flask equipped with a stirrer two addition funnels The cooling bath was removed water (100 mL) was added at room temperature stirred for 10 minutes The organic layer was separated the aqueous layer was extracted with DCM (3×100 mL) The combined organic layers were washed with brine (3×50 mL) dried over magnesium sulfate filtered concentrated The material was purified by silica gel chromatography (petroleum ether/ethyl acetate, 15/1)