Hydrochloric Acid → 2-(4'-(6-Carbamoyl-3,5-dimethylpyrazin-2-yl)-2,5-dichlorobiphenyl-4-yl)acetic acid

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Reaction Conditions

Reaction Steps

Powdered potassium hydroxide (56.1 mg, 1.00 mmol) was added in one portion to methyl 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2,5-dichlorobiphenyl-4-yl)acetate (Intermediate 4-1; 148 mg, 0.33 mmol) in tert-butanol (10 mL) at 55° C. The resulting solution was stirred at 55° C. for 45 minutes, 2M HCl (2 mL) was added and the mixture was evaporated to remove the organic solvent. The suspension was collected by filtration, washed with water (50 mL) and air dried to afford crude product as a pale yellow solid, which contained a minor impurity. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 0.1% formic acid) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2,5-dichlorobiphenyl-4-yl)acetic acid (79 mg, 55.2%) as a white solid.

Provenance & Evidence