Sodium Hydroxide → (S)-1-((Benzyloxy)carbonyl)-4,4-difluoropyrrolidine-2-carboxylic acid

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Reaction Steps

A solution of 5.6 grams of N-carbobenzyloxy-4,4-difluoro-L-proline, methyl ester in 50 ml. of methanol is treated dropwise with 11.5 ml. of 2 N sodium hydroxide solution at 0°-5°. The reaction mixture is left at 0° for 1 hour and is then allowed to warm to room temperature overnight. The reaction mixture is concentrated under reduced pressure to about one-half its original volume and is then diluted with 100 ml. of water. The aqueous reaction mixture is extracted with ether and the ether extracts discarded. The aqueous solution is acidified with cooling with dilute hydrochloric acid to pH 2 and is then extracted with ethyl acetate (3×50 ml.). The ethyl acetate extracts are combined and washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated to yield the desired product, N-carbobenzyloxy-4,4-difluoro-L-proline. It is purified by conversion to the cyclohexylamine salt, m.p. 180°-185° [α]D26 -24° (c=1%; ethanol).

Provenance & Evidence