Sodium Bicarbonate → N-[N2-(1(S)-Carboxy-3-phenylpropyl)-N6-glycyl-L-lysyl]-L-proline

Participants

Reaction Steps

A solution of 405 mg (1.0 mmol) of N-[N2 -(1(S)-carboxy-3-phenylpropyl)-L-lysyl]-L-proline and 252 gm (3.0 mmol) of sodium bicarbonate in 3 ml of water was treated with a solution of 272 mg (1.0 mmol) of N-t-butoxycarbonyl-glycine N-hydroxysuccinimide ester in 2 ml acetonitrile. The resulting clear solution was stirred at room temperature for 11/2 hours, concentrated in vacuo to 3/4 volume and acidified by dropwise addition of 2.5 N HCl. The resulting mixture was shaken with a small amount of ethyl acetate and the ethyl acetate/water layer decanted off a white, insoluble gum. The insoluble gum was flushed in vacuo with methanol and pumped out on an oil pump to provide 395 mg of crude product contaminated with a small amount of starting material. LH-20 Chromatograph (2.5×240 cm, methanol system) yield 305.6 mg of N-[N2 -(1(S)-carboxy-3-phenylpropyl)-N6 -(N-tert-butoxycarbonylglycyl)-L-lysyl]-L-proline. 305 mg (0.54 mmol) of the above intermediate was then dissolved in 8 ml trifluoroacetic acid (drying tube) and stirred at room temperature for 20 minutes. The reaction mixture was concentrated in vacuo, flushed 2x with ethyl ether and pumped out on an oil pump. The residual dry, white foam was dissolved in 8 ml of water and put on a column of 8 ml of Dowex 50W-X2(H+) resin. After aqueous washes, the product was eluted with water containing 2% pyridine, which after freeze-drying, provided 265 mg of N-[N2 -(1(S)-carboxy-3-phenylpropyl)-N6 -glycyl-L-lysyl]-L-proline that was single spot by tlc (ethyl acetate/pryridine/acetic acid/water (10:5:1:3) system) and had an excellent nmr in deuteromethanol (aromatic singlet at 7.2 ppm and the glycyl methylene at 3.7 ppm).

Provenance & Evidence