Diethyl Ether → tert-Butyl 3-hydroxy-3-methylpyrrolidine-1-carboxylate

Participants

Reaction Steps

To a 30 L reaction kettle was added 4 L dry THF at −10° C. After stirring, to the mixture were added ZnCl2 (118 g, 0.86 mol) and LiCl (402 g, 9.5 mol). After half an 0.5 hour, to the resulting mixture was slowly added a solution of MeMgBr (3 mol/L) in diethyl ether (6.4 L, 19.2 mol) dropwisely. The stirring was continued for half an hour. To the resulting mixture was slowly added a solution of tert-butyl 3-oxopyrrolidine-1-carboxylate (1600 g, 8.6 mol) in THF dropwisely. After the completion of reaction by HPLC detection, to the system was dropwisely added a saturated NH4Cl solution to quench off the reaction. The reaction was extracted with ethyl acetate. The organic phase was washed with a saturated aqueous NaCl solution, dried over anhydrous sodium sulfate, and evaporated to remove the solvent to produce tert-butyl 3-hydroxy-3-methylpyrrolidine-1-carboxylate as a pale yellow solid (1450 g) in a yield of 83.8%.

Provenance & Evidence