Triethylamine → Ethyl 1-(4-cyclopropoxybenzamido)cyclopropanecarboxylate

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Reaction Steps

To a 0° C. suspension of 4-cyclopropoxybenzoic acid (24.5 g, 137.3 mmol) in dichloromethane (350 mL) containing 2 drops of DMF, slowly add oxalyl chloride (23.8 mL, 274.7 mmol). After addition, remove the cooling bath and stir for 2 hours. Concentrate the material to dryness under reduced pressure. Dissolve the residue in dichloromethane (500 mL), and then add ethyl 1-aminocyclopropanecarboxylate hydrochloride (Indofine #04-265, 24.9 g, 150.5 mmol) and triethylamine (57.2 mL, 410.4 mmol). Stir the mixture at ambient temperature for approximately 16 hours. Wash the mixture once with 10% NaHSO4 (250 mL). Separate the organic portion and extract the aqueous portion 2× with dichloromethane (200 mL). Combine the organic, dry over sodium sulfate, filter, and concentrate under reduced pressure. Purify the crude mixture by flash chromatography (0% to 45% EtOAc/Hex) to give the title compound (33.7 g, 85%): MS (m/z): 290 (M+1).

Provenance & Evidence