Hydrochloric Acid → Ethyl 1-[(4-ethoxybenzoyl)amino]cyclopropanecarboxylate

Participants

Reaction Steps

Add oxalyl chloride (189 mL, 2.17 mol) to 4-ethoxybenzoic acid (334.5 g, 1.99 mol) and N,N-dimethylformamide (1 mL) in dichloromethane (3 L). After 1 hr at 25-26° C., concentrate the mixture under reduced pressure until a constant weight is achieved. Stir ethyl 1-aminocyclopropanecarboxylate hydrochloride (300 g, 1.81 mol) and dichloromethane (2.5 L) in an ice water bath. Add triethylamine (631 mL, 4.53 mol) and then add a solution of the acid chloride (ca 380 g) in dichloromethane (500 mL). Stir the reaction mixture for approximately 16 hours at ambient temperature. Dilute the reaction with aqueous 1N hydrochloric acid (1 L). Extract the aqueous layer with dichloromethane (1 L). Wash the organic layer with water (2 L) and brine (2 L). Dry the solution over sodium sulfate, filter, and concentrate under reduced pressure. Slurry the residue in hexanes and filter to give the title compound (478 g, 95%) as an ivory powder: MS (mass spectrometry) (m/z): 278 (M+1).

Provenance & Evidence