Ethyl chloroformate → HCID 58293818, compound

Participants

Reaction Steps

To a solution of Compound 1040 (35.2 g, 176.6 mmol) in 1:1 water/THF (1. L) was added solid sodium bicarbonate (32.6 g, 388.6 mmol) and ethyl chloroformate (20.3 mL, 212.0 mmol). The reaction was stirred at room temperature overnight, at which point LCMS indicated complete disappearance of starting material. The reaction mixture was diluted with water, extracted with ethyl acetate, and the volatiles removed under reduced pressure to give methyl 3-(ethoxycarbonyl(thiophen-2-ylmethyl)amino)propanoate as a pale yellow oil (Compound 1041, 19.9 g, 41%); 1H NMR (300 MHz, CDCl3): δ 7.20-7.12 (m, 1H), 6.94-6.83 (m, 2H), 4.56 (s, 2H), 4.10 (td, J=14.5, 7.3 Hz, 2H), 3.52 (s, 3H), 3.46 (t, J=6.6 Hz, 2H), 2.47-2.39 (m, 2H), 1.97 (s, H) and 1.24-1.15 (m, 3H) ppm. The aqueous layer contained some 3-(ethoxycarbonyl(thiophen-2-ylmethyl)amino)propanoic acid (Compound 1042) resulting from hydrolysis of the methyl ester. Compound 1042 could be isolated by adjusting the pH of the aqueous layer to 2 with 6M HCl followed by extraction with 10% n-BuOH in chloroform, which after concentration gave the carboxylic acid as a pale yellow oil (17.33 g).

Provenance & Evidence