Benzyl 6-oxa-3-azabicyclo(3.1.0)hexane-3-carboxylate → benzyl (3S,4R)-3-hydroxy-4-methylpyrrolidine-1-carboxylate

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Reaction Conditions

Reaction Steps

To a stirred suspension of CuI (10.2 g, 54 mmol) in ether (120 mL) at −10° C. was added dropwise MeLi (73 mL, 109 mmol, 1.5 M in ether) ensuring that the temperature remained below −5° C. The resulting solution was stirred at −10° C. for 20 min and a solution of phenylmethyl 6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate (Example 113) (5 g, 23 mmol) in ether (50 mL) was added, maintaining the temperature below −2° C. The reaction was stirred at −10° C. for 1 hour after which time it was quenched with water and partitioned with DCM. A standard work up yielded phenylmethyl (trans)-3-hydroxy-4-methyl-1-pyrrolidinecarboxylate, which was purified and subjected to chiral chromatography, producing two enantiopure compounds of undetermined absolute stereochemistry. (Yield of E1=1.55 g, yield of E2=1.58 g).

Provenance & Evidence