Potassium Hydroxide → 2-(2-(4'-(6-Carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetamido)-2-methylpropanoic acid

Participants

Reaction Conditions

Reaction Steps

Potassium hydroxide (109 mg, 1.94 mmol) was added in one portion to methyl 2-(2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetamido)-2-methylpropanoate (Intermediate 14-1; 319.5 mg, 0.65 mmol) in t-BuOH (4164 μL) at room temperature. The resulting solution was stirred at 45° C. for 5 hours and a precipitate formed. The reaction mixture was quenched with 2M HCl (5 mL), The reaction mixture was evaporated to dryness and redissolved in water (10 mL), and filtered through nylon, washed with water and dried under vacuum. 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-(2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetamido)-2-methylpropanoic acid (18.20 mg, 5.86%) as a white solid.

Provenance & Evidence