Trifluoroacetic acid → HCID 70486117, compound

Participants

Reaction Steps

A mixture of N-t-butoxycarbonyl-L-alanyl-L-proline ethanesulphonamide (22.5 g.) and trifluoroacetic acid (60 ml.) was stirred at laboratory temperature for 1 hour, the excess of trifluoroacetic acid was removed by evaporation and toluene was twice added and removed by evaporation, finally at 0.5 mm.Hg. A solution of the L-alanyl-L-proline ethanesulphonamide trifluoroacetate thus obtained in ethanol (350 ml.) was cooled to 10° C. and triethylamine (17 ml.), a solution of ethyl 2-oxo-4-phenylbutyrate (18.6 g.) in ethanol (50 ml.), powdered activated 3 Å molecular sieve (75 g.) and Raney nickel (15 g.) were successively added. The mixture was stirred under an atmosphere of hydrogen at laboratory temperature and pressure for 20 hours and then filtered through a filter-aid, and the filtrate was evaporated to dryness. The residue was shaken with diethyl ether and 10% aqueous potassium carbonate solution and the aqueous layer was separated, washed with diethyl ether, acidified to pH 3 with citric acid and extracted four times with ethyl acetate. The combined extracts were dried and evaporated to dryness and there were thus obtained the mixed isomers of N-(1-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-L-proline ethanesulphonamide in a ratio (as shown by high pressure liquid chromatography) of approximately 22:3 by weight, the more active (as an inhibitor of ACE) isomer predominating.

Provenance & Evidence