2,6-Difluoro-4-methoxybenzeneboronic acid → 1-Cyclohexyl-3-(3,5-dichloro-2',6'-difluoro-4'-methoxy-biphenyl-4-ylmethyl)-pyrrolidin-2-one

Participants

Reaction Steps

Using the procedure to synthesize Example 81 and using reagents 3,5-dichloro-4-((1-cyclohexyl-2-oxopyrrolidin-3-yl)methyl)phenyl trifluoromethanesulfonate (Example 240) (500 mg, 1.0 mmol) and 2,6-difluoro-4-methoxyphenylboronic acid (590 mg, 3.2 mmol) affords 494 mg (100%) of 1-Cyclohexyl-3-(3,5-dichloro-2′,6′-difluoro-4′-methoxy-biphenyl-4-ylmethyl)-pyrrolidin-2-one. Charge a flask with 1-cyclohexyl-3-(3,5-dichloro-2′,6′-difluoro-4′-methoxy-biphenyl-4-ylmethyl)-pyrrolidin-2-one (500 mg, 1.1 mmol), dissolve in dry methylene chloride (10 mL) and cool to 0° C. under nitrogen. Add BBr3 (0.25 mL, 2.7 mmol) and stir at 0° C. for 1.5 hours. Pour into saturated aqueous sodium bicarbonate and extract with methylene chloride. Dry over sodium sulfate, filter and concentrate in vacuo to yield 470 mg (97%) of the title compound.

Provenance & Evidence