tert-Butyl (2S)-2-isopropyl-4-oxopyrrolidine-1-carboxylate → tert-butyl (2S)-4-hydroxy-4-methyl-2-(propan-2-yl)pyrrolidine-1-carboxylate

HRID 81131Notes

Reaction equation

[O:1]=[C:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([CH:14]([CH3:16])[CH3:15])[CH2:3]1.[CH3:17][Mg]Br>C1COCC1>[OH:1][C:2]1([CH3:17])[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:11])([CH3:13])[CH3:12])=[O:8])[C@H:4]([CH:14]([CH3:16])[CH3:15])[CH2:3]1

Participants

Conditions

Temperature: -78 °C

Procedure

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.

Workup

temperaturebefore warming to room temperature
stirringstirring for an additional 2 hours
customThe reaction was quenched by slowly adding saturated aqueous ammonium chloride at 0° C
extractionextracted with ethyl acetate (2×)
washThe combined organic layers were washed with brine
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe residue was purified by silica gel chromatography (0-80% ethylacete/hexanes, linear gradient)

Sources & evidence

ORD record: ord-6aa0d4f5be7b4c2097107ab7a0a3b04b
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846657B2

Reaction notes

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