Sodium hydride → (Z)-(S)-2-(3-Benzyloxypropyl)-5-tert-butoxycarbonylamino-hex-2-enedioic acid 6-tert-butyl ester 1-ethyl ester

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Reaction Conditions

Reaction Steps

A solution of 5-Benzyloxy-2-(diethoxyphosphoryl)-pentanoic acid ethyl ester (1.36 g, 3.65 mmol) in dry THF (5 mL) was added dropwise at 0° C. to a solution of sodium hydride (0.18 g, 7.46 mmol) in dry THF (3 mL). After stirring for 15 min tert-Butyl (2S)-2-[(tert-butoxycarbonyl)amino]-4-oxobutanoate (Example 1c) (1.0 g, 3.66 mmol) was added as a solution in dry THF (5 mL) dropwise to the reaction mixture. After stirring for 90 min at 0° C. the reaction was quenched by addition of saturated sodium bicarbonate solution (50 mL). After phase separation the aqueous layer was extracted with ethyl acetate (3×50 mL) and the combined organic layers were dried over sodium sulphate, concentrated under reduced pressure and the residue was purified by column chromatography on silica gel (hexane/ethyl acetate gradient) to give (Z)—(S)-2-(3-Benzyloxypropyl)-5-tert-butoxycarbonylamino-hex-2-enedioic acid 6-tert-butyl ester 1-ethyl ester and (E)-(S)-2-(3-Benzyloxypropyl)-5-tert-butoxycarbonylamino-hex-2-enedioic acid 6-tert-butyl ester 1-ethyl ester as a mixture of diastereomers.

Provenance & Evidence