Hydrochloric Acid → Racemic 2-(4'-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)propanoic acid

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Reaction Conditions

Reaction Steps

Powdered potassium hydroxide (331 mg, 5.90 mmol) was added in one portion to methyl 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)propanoate (Intermediate 8-1; 834 mg, 1.97 mmol) in tert-butanol (20 mL) at 45° C. The resulting solution was stirred at 45° C. for 30 minutes. 2M HCl (6 mL) was added and the mixture was evaporated to remove the organic solvent. The suspension was collected by filtration, washed with water and dried under vacuum to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in DCM. Fractions containing the desired compound were evaporated to dryness to afford racemic 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)propanoic acid (603 mg, 74.8%) as a white solid. This was purified by preparative chiral-HPLC on a OJ column, eluting isocratically with 30% EtOH in isohexane (acidified with AcOH) as eluent. The fractions containing the desired compound were evaporated to dryness to afford:

Provenance & Evidence