2-Thiopheneacetic acid → 1-[3-(4-tert-butylbenzoyl)propionyl]-L-proline

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Reaction Steps

As for example 85, 14 g. of 3-(4-tert-butylbenzoyl)-propionic acid is reacted with 6.9 g. of N-hydroxysuccinimide in the presence of 12.36 g. of N,N-dicyclohexylcarbodiimide to give 15.5 g. of 3-(4-tert-butylbenzoyl)propionic acid, N-hydroxysuccinimide ester, m.p. 135°-138° C. The preceding compound is added to a solution of 8.05 g. of L-proline and 11.76 g. of sodium bicarbonate in 400 ml. of ethanol-water (1:1). The mixture is stirred overnight, filtered and the filtrate concentrated under vacuum. The mixture is acidified with concentrated hydrochloric acid and extracted with dichloromethane. The solvent is removed to give an amber gum which chromatographed on 150 g. of silica gel with hexane-ethyl acetate (1:1) containing 2% acetic acid as solvent. From the column is obtained 12.4 g. of glass. To a solution of 9.8 g. of the preceding glass in 150 ml. of acetic acid is added 4.8 g. of bromine. The mixture is stirred overnight, concentrated and poured into ice and water. The mixture is extracted with dichloromethane and the extract concentrated to give 12.1 g. of a glass. The preceding glass is added to a solution of 1.94 g. of sodium methoxide and 4.56 g. of thiolacetic acid in 50 ml. of ethanol. After stirring for 2 hours, 1 ml. of acetic acid is added and the mixture diluted with water. The mixture is extracted with dichloromethane, the extract washed with water, dried (MgSO4) and the solvent removed to give 12 g. of product as a yellow glass.

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