tert-Butyl 6-Oxa-3-azabicyclo(3.1.0)hexane-3-carboxylate → tert-butyl (3S,4R)-3-hydroxy-4-Methylpyrrolidine-1-carboxylate

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Reaction Conditions

Reaction Steps

Cool down a suspension of copper (I) iodide (1 g, 5.5 mmol) in dry diethyl ether (13 mL) under nitrogen to −10° C. with a saturated aqueous sodium chloride/ice bath and add methyllithium (1.6 M in diethyl ether, 6.8 mL, 10.9 mmol) dropwise to maintain the temperature at −10° C. Stir for 20 min at this temperature and add a solution of 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester (430 mg, 2.32 mmol) in dry diethyl ether (5 mL). Stir for 1 h at −10° C. then add water (5 mL) dropwise and dichloromethane (5 mL), filter the resulting mixture through a pad of Celite® and wash thoroughly with dichloromethane. Separate the aqueous and organic phases and extract with 30:70 isopropanol:chloroform and wash with saturated aqueous sodium chloride, dry (magnesium sulfate) and concentrate to give trans-3-hydroxy-4-methylpyrrolidine-1-carboxylic acid tert-butyl ester which can be used without further purification (360 mg, 77%). 1H NMR (300 MHz, CDCl3) δ 3.84-3.91 (1H, m), 3.48-3.62 (2H, m), 3.10-3.23 (1H, m), 2.88-3.02 (1H, m), 1.98-2.12 (1H, m), 1.39 (9H, s), 0.95 (3H, d, J=6.97 Hz), MS (ES): m/z=224 [M+Na].

Provenance & Evidence