Hydrochloric Acid → Methyl 2-{[2-(3,5-difluorophenyl)-2-oxoethyl]amino}-2-ethylbutanoate

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Reaction Conditions

Reaction Steps

A mixture of methyl 2-amino-2-ethylbutanoate hydrochloride from Step A (2.10 g, 11.6 mmol), 3,5-difluorophenacyl bromide (2.99 g, 12.7 mmol), and NaHCO3 (2.43 g, 28.9 mmol) in DMF (20 mL) was stirred at 45° C. for 1 h, and at ambient temperature for 2 h. 1 N aqueous HCl (50 mL) was added and the mixture was extracted with EtOAc (75 mL) and this organic extract was discarded. The aqueous layer was adjusted to pH 10 by addition of saturated aqueous Na2CO3 (150 mL) was added and the mixture was extracted with EtOAc (3×75 mL). The combined organic layers were treated with CF3CO2H (1.5 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by HPLC using a reversed phase C18 column and eluting with a gradient of H2O:CH3CN:CF3CO2H—90:10:0.1 to 5:95:0.1. The product-containing fractions were combined, basified with saturated aqueous NaHCO3, and extracted with EtOAc. The organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo to give the title compound. MS: m/z=300 (M+1).

Provenance & Evidence