Citric Acid → Methyl(1R,2R,4S,5S,6R)-2-{[tert-butyl(dimethyl)silyl]oxy}-6-fluoro-4-hydroxybicyclo[3.1.0]hexane-6-carboxylate

Participants

Reaction Conditions

Reaction Steps

A THF (270 mL) solution of the compound of Formula 13a thus obtained was cooled to −50° C., and 210 mL (197.40 mmol) of a 0.94 mol/L triethylaluminum hexane solution was added thereto over 30 minutes while keeping the internal temperature between −55° C. and −50° C. After stirring at −50° C. for 30 minutes, 143 mL (228.80 mmol) of a 1.6 mol/L lithium hexamethyldisilazide (LiHMDS) hexane solution was added thereto over 10 minutes while keeping the internal temperature between −50° C. and −40° C. After stirring at −50° C. for 2 hours the reaction mixture was added over 20 minutes to 265.08 g of a 25% citric acid aqueous solution cooled at 5° C. 270 mL of ethyl acetate was added to the reaction mixture, which was stirred and then separated. Extraction was carried out with 100 mL of ethyl acetate, the organic layers were combined, washed with 50 mL of water, and then concentrated under reduced pressure, thus giving 56.65 g of methyl (1R,2R,4S,5S,6R)-2-[(tert-butyl(dimethyl)silyl]oxy)-6-fluoro-4-hydroxybicyclo[3.1.0]hexane-6-carboxylate (14a) as a brown oily material.

Provenance & Evidence