1,2-Dichloroethane → HCID 19705517, compound

Participants

Reaction Steps

A cold (0° C.) solution of α-[2-[(3,4-difluorobenzoyl)amino]ethyl]-3-(3-hydroxypropyl)-2-oxo-1-(2-phenylethyl)-3-pyrrolidineacetic acid (586 mg, 1.20 mmol) in 2:1 CH2Cl2 /DMF (7.5 mL) is treated with HOBT (195 mg, 1.44 mmol), EDC (276 mg, 1.44 mmol), and 4-methylmorpholine (158 μL, 1.44 mmol). The ice bath is removed, and after 1 hour, O-benzylhydroxylamine HCl (287 mg, 1.80 mmol) and a second portion of 4-methylmorpholine (198 μL, 1.80 mmol) are added. The solution is stirred overnight at room temperature under N2. The solution is diluted with H2O (25 mL) and extracted into CH2Cl2 (3×50 mL). The extracts are combined, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to provide an oil. The residual oil is reconstituted in EtOAc (50 mL) and washed with 1N HCl (10 mL), 1N NaOH (10 mL), H2O (10 mL), and brine (10 mL). The organic layer is dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to give 603 mg of a white foam. The material is purified by silica gel chromatography (25 g SG; EtOAc) to provide 433 mg (62%) of the title compound as a white, amorphous solid:

Provenance & Evidence