Acetic Acid → 1-(4'-(6-Carbamoyl-3,5-dimethylpyrazin-2-yl)-2,6-difluorobiphenyl-4-yl)cyclopropanecarboxylic acid

Participants

Reaction Conditions

Reaction Steps

Powdered potassium hydroxide (91 mg, 1.62 mmol) was added in one portion to methyl 1-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2,6-difluorobiphenyl-4-yl)cyclopropanecarboxylate (Intermediate 28-1; 142 mg, 0.32 mmol) in tert-butanol (10 mL). The resulting yellow cloudy suspension was stirred at 40° C. for 1 hour. The reaction mixture was quenched with acetic acid (0.149 mL, 2.60 mmol) in ethanol (2 mL) and the resulting solution stirred for a further 10 minutes before being evaporated to dryness. The resulting solid was partitioned between water (20 mL) and ethyl acetate (20 mL). An insoluble solid was filtered off. The organic layer was separated and the aqueous re-extracted with ethyl acetate (20 mL). The combined organics were evaporated in vacuo to give crude product as an off white solid. The crude solid was triturated with mixture of DCM (3 mL) and methanol (3 mL) to give a solid which was collected by filtration and dried under vacuum to give 1-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2,6-difluorobiphenyl-4-yl)cyclopropanecarboxylic acid (52.0 mg, 37.8%) as a white solid.

Provenance & Evidence