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

HRID 1366480Notes

Reaction equation

[Li][CH3:2].[CH:3]12[O:8][CH:7]1[CH2:6][N:5]([C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10])[CH2:4]2>CCOCC.[Cu]I>[OH:8][C@H:7]1[C@H:3]([CH3:2])[CH2:4][N:5]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:6]1

Participants

Conditions

Temperature: -10 °C

Procedure

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).

Workup

customremained below −5° C
temperaturemaintaining the temperature below −2° C
stirringThe reaction was stirred at −10° C. for 1 hour after which time it
customwas quenched with water
custompartitioned with DCM

Sources & evidence

ORD record: ord-9c7e57ae86614790be4a9539a685916e
Source dataset: uspto-grants-2011_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07893056B2

Reaction notes

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