4-Ethoxybenzoic acid → Ethyl 1-[(4-ethoxybenzoyl)amino]cyclopropanecarboxylate

Participants

Reaction Steps

Combine 4-ethoxybenzoic acid (10.0 g, 60.18 mmol), ethyl 1-aminocyclopropanecarboxylate hydrochloride (commercially available, 10.96 g, 66.19 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) (13.84 g, 72.21 mmol), and 1-hydroxybenzotriazole (HOBT) (9.76 g, 72.21 mmol) in tetrahydrofuran (500 mL). Add diisopropylethylamine (DIEA) (23.09 mL, 132.39 mmol) over 3-5 minutes and stir the reaction for approximately 16 hours at ambient temperature under nitrogen. Dilute the mixture with ethyl acetate, wash with dilute HCl, dilute NaHCO3, and then brine, dry over sodium sulfate, and concentrate the organic layer under reduced pressure. Purify the residue by recrystallization from ethanol to give the title compound (13.93 g, 84%) as a white solid: MS (m/z): 278 (M+1).

Provenance & Evidence