2-Fluoroethyl bromide → HCID 17747540, compound

Participants

Reaction Conditions

Reaction Steps

Treat a solution of 1-cyclohexyl-3-[3,5-dichloro-4′-(piperazine-1-carbonyl)-biphenyl-4-ylmethyl]-pyrrolidin-2-one (0.67 g, 1.30 mmol) in dimethylformamide (7 mL) with 1-bromo-2-fluoroethane (0.99 g, 7.80 mmol) and heat to 55° C. for 16 hours under a nitrogen atmosphere. Cool the reaction, dilute with ethyl acetate and wash with saturated aqueous sodium bicarbonate then water. Dry the organic layer with sodium sulfate and purify the crude product by silica gel chromatography using a gradient of 0 to 10% methanol in dichloromethane to afford 0.47 g (64%) of the title compound in its racemic form. Separate into the enantiomers by chiral HPLC (Chiralpak AD 8×33 cm column, isocratic 90:10 3 A ethanol:acetonitrile with 0.2% dimethylethylamine, 400 mL/min, 300 nM UV) to afford 286 mg of Isomer 1 (>99% ee) and 283 mg of Isomer 2 (98.9% ee): MS (m/z): 560. Check the purity of each isomer using chiral HPLC (Chiralpak AD-H 4.6×150 mm column, isocratic 90:10 3A ethanol:acetonitrile with 0.2% dimethylethylamine, 0.6 mL/min, 270 nM).

Provenance & Evidence