Powdered potassium hydroxide (0.045 g, 0.81 mmol) was added in one portion to methyl 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2,2′-dichlorobiphenyl-4-yl)acetate (Intermediate 22-1; 0.12 g, 0.27 mmol) in tert-butanol (2.00 mL) at 40° C. under nitrogen. The resulting suspension was stirred at 40° C. for 20 minutes. A thick precipitate formed so the reaction was quenched with HCl (1.620 mL, 1.62 mmol) in ethanol (20.0 mL) and the resulting solution stirred for a further 20 minutes before being evaporated to dryness. The resulting solid was partitioned between water (5 mL) and EtOAc (15 mL). The aqueous layer showed a pH=4˜5. The organic layer was separated and the aqueous re-extracted with EtOAc (2×5 mL). The combined organics were washed with brine (15 mL), dried over MgSO4 and evaporated in vacuo to give product. This was washed with ether (5 mL) and dried under vacuum at room temperature to give an off white solid. The crude product was purified by preparative HPLC (Waters—Xbridge Prep C18 5 μm), using decreasingly polar mixtures of water (containing 0.1% ammonia) and {MeOH(3):MeCN(1)} as eluents. Fractions containing the desired compound were evaporated to dryness to afford 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2,2′-dichlorobiphenyl-4-yl)acetic acid (0.063 g, 51.7%) as a colourless solid.
