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

Participants

Reaction Conditions

Reaction Steps

Powdered potassium hydroxide (106 mg, 1.89 mmol) was added in one portion to methyl 2-(2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetamido)acetate (Intermediate 20-1; 294 mg, 0.63 mmol) in tert-butanol (4062 μL) at 45° C. The resulting solution was stirred at 45° C. for 150 minutes, a thick white suspension slowly precipitate formed. 2M HCl (5 mL) was added and the mixture was evaporated to remove the organic solvent. The reaction mixture was diluted with EtOAc and water, the organic layer was collected, dried with MgSO4 and evaporated to afford crude product. This 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-(2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetamido)acetic acid (56.8 mg, 19.92%) as a white solid.

Provenance & Evidence