Triethylamine → (1S,2R,3S,4S,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-{[(3,4-difluorophenyl)sulfanyl]methyl}-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid

Participants

Reaction Conditions

Reaction Steps

Triethylamine (407.27 mL, 2.92 mol) and [2-(tert-butoxycarbonyloxyimino)-2-phenylacetonitrile] (308.39 g, 1.25 mol) are added to a suspension of (1S,2R,3S,4S,5R,6R)-2-amino-3-{[(3,4-difluorophenyl)sulfanyl]methyl}-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid (300.00 g, 834.84 mmol) in 1,4-dioxane (500.9 mL) and water (500.9 mL) at 25° C. The mixture is warmed to 50° C. After 12 hours, the reaction is cooled to 25° C., diluted with water (2.5 L), and washed with methyl tert-butyl ether (6×1 L). Basify the aqueous phase with a solution of aqueous. 1N HCl until pH=2, and extract with ethyl acetate (3×2 L). The combined ethyl acetate extracts are washed with brine, dried over MgSO4, and concentrated in vacuo to yield the title compound (250 g, 65% yield). MS (m/z): 360 (M+-Boc).

Provenance & Evidence