Ethyl alpha-oxobenzenebutanoate → Ammonium Hydroxide

Participants

Reaction Steps

Dissolve the 7-[(S)-alanyl]-1,4-dithia-7-azaspiro[4.4]nonane-8(S)-carboxylic acid hydrobromide (prepared in paragraph E next above) in 100 ml of absolute methanol. Add 0.5 g of 2-oxo-4-phenylbutyric acid, ethyl ester and 10 ml of 3A molecular sieve pellets and stir the mixture at room temperature for eighteen hours. Filter the reaction mixture and treat the filtrate with 0.30 g of sodium cyanoborohydride at room temperature for two hours. Concentrate the mixture under nitrogen and dilute the oil with 5% hydrochloric acid to pH 2 to 4 and stir at room temperature for one hour. Adjust the pH of the solution to pH 8 with 2.5 N sodium hydroxide solution and absorb the solution in 150 ml of XAD-2 resin. Elute the resin with 800 ml of water and then with 800 ml of methanol. Concentrate the methanol solution, place the residue on a column of silca gel (100 g, 60-200 mesh) and elute with chloroform:isopropanol:7% ammonium hydroxide 1:1:1 (organic layer) to obtain 7-[N-(1-carboethoxy-3-phenylpropyl)-(S)-alanyl]-1,4-dithia-7-azaspiro[4.4]nonane-8(S)-carboxylic acid, a white solid, m.p. 56°-60° C., [α]D26 -25.5° (ethanol).

Provenance & Evidence