Diisobutylaluminum hydride → (1R,2S,5R)-tert-butyl 2-(benzyloxycarbonylamino)-7-hydroxy-6-aza-bicyclo[3.2.1]octane-6-carboxylate

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Reaction Conditions

Reaction Steps

To a cooled (0° C.) solution of (1R,2S,5R)-2-benzyloxycarbonylamino-7-oxo-6-aza-bicyclo[3.2.1]octane-6-carboxylic acid tert-butyl ester (4.6 g, 12.3 mmol) in CH2Cl2 (100 mL) was added DIBAL-H (37 mL of a 1.0 M solution in THF). The mixture was stirred for 105 min at 0° C. The reaction was quenched with 1N HCl and extracted with EtOAc (2×). The organic extracts were combined, washed with brine, dried,(Na2SO4), filtered, and concentrated in vacuo to afford tert-butyl (1R,2S,5R,7R/S)-2-(benzyloxycarbonylamino)-7-hydroxy-6-aza-bicyclo[3.2.1]octane-6-carboxylate as a mixture of diastereomers. MS found: (M−H2O+H)+=359.2. This material was dissolved in THF (20 mL) and added by cannula (6 mL THF rinse) to a pre-mixed (15 min), pre-cooled (0° C.) solution of ethyltriphenylphosphonium iodide (6.4 g, 14.8 mmol) and KHMDS (31 mL of a 0.5 M solution in toluene). The reaction was stirred for 25 min at 0° C. before being quenched with the addition of sat. NH4Cl. The biphasic mixture was extracted with EtOAc (2×). The organic extracts were combined, washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo. Purification of the residue via flash chromatography afforded the desired [(1R,3R,4S)-(4-benzyloxycarbonyl-amino-3-propenyl-cyclohexyl)-carbamic acid tert-butyl ester as a colorless oil (3.44 g, 72% yield). MS found: (M+H)+=389.3.

Provenance & Evidence