Water → Di-tert-butyl (1S,2R,3S,4R,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-[(3,4-dichlorobenzyl)oxy]-4-hydroxybicyclo[3.1.0]hexane-2,6-dicarboxylate

Participants

Reaction Steps

To a solution of di-tert-butyl (1S,2R,3S,4R,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3,4-dihydroxybicyclo[3.1.0]hexane-2,6-dicarboxylate (450 g, 1.05 mol) in dichloromethane (4.50 L) at room temperature is sequentially added 3,4-dichlorobenzyl bromide (144.73 mL, 238.80 g, 995.32 mmol), tetra-N-butylammonium chloride (58.24 g, 209.54 mmol), and a 50% wt/wt aqueous solution of sodium hydroxide (829.80 mL, 15.72 mol). After 7 hours, dilute the reaction with water (1 L) and separate the phases. Extract the organic phase with brine (500 mL), dry over anhydrous MgSO4, filter and concentrate. Purify the residue by chromatography (2.5 kg of SiO2; eluent: hexane/ethyl acetate 12:1 to 0:1) to give the title compound (539 g, 72% yield).

Provenance & Evidence