Triethylamine → (1S,2R,3S,4S,5R,6R)-2-[(Tert-butoxycarbonyl)amino]-3-[(3,4-dichlorobenzyl)oxy]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid

Participants

Reaction Conditions

Reaction Steps

Triethylamine (212.80 mL, 154.49 g, 1.53 mol) and 2-(tert-butoxycarbonyloxyimino)-2-phenylacetonitrile (125.33 g, 508.90 mmol) are added sequentially to a suspension of (1S,2R,3S,4S,5R,6R)-2-amino-3-[(3,4-dichlorobenzyl)oxy]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylic acid hydrochloride (140 g, 339 mmol) in 1,4-dioxane (203.56 mL), and water (0.6 mL/mmol-pure-LR, 203.56 mL), at ambient temperature. After 4.5 hours, add additional 2-(tert-butoxycarbonyloxyimino)-2-phenylacetonitrile (25.07 g, 101.78 mmol) and triethylamine (23.64 mL, 17.17 g, 169.63 mmol) to the reaction and stir at 50° C. overnight. Cool to 23° C., dilute with water (500 mL), and wash with methyl tert-butyl ether (6×500 mL). Dilute the aqueous phase with 10% aq. HCl (300 mL; final pH=2) and extract with ethyl acetate (2×500 mL). The ethyl acetate extracts are dried over MgSO4 and concentrated in vacuo to yield the title compound (148.3 g, 92% yield).

Provenance & Evidence