Potassium Hydroxide → (2RS,5RS)-3-{3-[2-(2-tert-butoxycarbonyl-5-phenyl-1-pyrrolidinyl)-2-oxoethyl]ureido}benzoic acid

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Reaction Conditions

Reaction Steps

0.9 g of potassium hydroxide dissolved in 60 cm3 of distilled water is added to a solution of 8 g of tert-butyl (2RS,5SR)-1-{2-[3-(3-ethoxycarbonylphenyl)ureido]acetyl}-5-phenylprolinate in 120 cm3 of methanol. The reaction mixture is stirred for 3 hours at a temperature in the vicinity of 25° C. then concentrated to 50 cm3 under reduced pressure. The solution obtained is diluted with 30 cm3 of water, washed with 2 times 50 cm3 of ethyl acetate, acidified to a pH of 2 with a 4N aqueous hydrochloric acid solution and extracted with 3 times 100 cm3 of dichloromethane. The organic phases are combined, washed with 2 times 50 cm3 of water, dried over magnesium sulphate and concentrated to dryness under reduced pressure at a temperature in the vicinity of 40° C. The crude product obtained is purified by chromatography on silica [eluent: dichloromethane/methanol (90/10 by volume)]. The fractions containing the expected product are combined and concentrated to dryness under reduced pressure. After recrystallization in ethyl acetate, 4.5 g of (2RS,5SR)-3-{3-[2-(2-tert-butyoxycarbonyl-5-phenyl-1-pyrrolidinyl)-2-oxoethyl]ureido}benzoic acid, melting at 236° C., are obtained.

Provenance & Evidence