Lithium tri-s-butylborohydride → Bis[(2-fluorophenyl)methyl](1S,2S,4S,5R,6R)-2-(tert-butoxycarbonylamino)-4-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylate

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Reaction Steps

Add 1M L-selectride solution in THF (6.78 mL, 6.78 mmol) dropwise to a stirred solution of bis[(2-fluorophenyl)methyl](1S,2S,5R,6R)-2-(tert-butoxycarbonylamino)-4-oxo-bicyclo[3.1.0]hexane-2,6-dicarboxylate (2.33 g, 4.52 mmol) in tetrahydrofuran (20.3 mL) at −78° C. Stir the resulting orange mixture under nitrogen for 1 hour 45 minutes. Quench with a saturated solution of sodium hydrogen carbonate at −78° C. Dilute with water and ethyl acetate. Separate the layers and wash the organic phase with brine and water. Dry over sodium sulfate, filter and concentrate to dryness to give the crude material as pale yellow oil contaminated with approximately 6% of the minor isomer bis[(2-fluorophenyl)methyl](1S,2S,4R,5R,6R)-2-(tert-butoxycarbonylamino)-4-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylate as detected by MS. Combine the crude material with a second batch similarly prepared from bis[(2-fluorophenyl)methyl](1S,2S,5R,6R)-2-(tert-butoxycarbonylamino)-4-oxo-bicyclo[3.1.0]hexane-2,6-dicarboxylate (0.23 g, 0.44 mmol). Purify the combined material by flash chromatography eluting with ethyl acetate:hexane (20:80 to 50:50) to give the title product as a single isomer (2.49 g, 4.81 mmol). MS (m/z): 540 (M+23).

Provenance & Evidence