Hydrochloric Acid → Methyl 1-((2-(3,5-difluorophenyl)-2-oxoethyl)amino)cyclopentanecarboxylate

Participants

Reaction Steps

A mixture of methyl 1-aminocyclopentanecarboxylate hydrochloride (10.0 g, 55.7 mmol, described in Intermediate 25), 3,5-difluorophenacyl bromide (14.4 g, 61.2 mmol), and Na3PO4 (22.8 g, 139 mmol) in DMF (100 mL) was stirred at ambient temperature for 3.5 h. The reaction mixture was acidified with 1 N aqueous HCl and the mixture was extracted with EtOAc (200 mL) and this organic extract was discarded. The aqueous layer was adjusted to pH 8-9 by addition of saturated aqueous NaHCO3 and the mixture was extracted with EtOAc (3×250 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc—90:10 to 50:50, to give the title compound. MS: m/z=298 (M+1).

Provenance & Evidence