Hydrochloric Acid → (1S,4R)-4-(5-{3-cyclopropyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}-1,3-thiazol-2-yl)-4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of the product from Step 1 (41.3 mg, 0.084 mmol) in tetrahydrofuran (0.4 mL) and methanol (0.8 mL) was added sodium hydroxide (1 M in water, 0.153 mL, 0.153 mmol). The reaction mixture was heated to 120° C. for 10 minutes in a microwave oven. An additional charge of sodium hydroxide was added (1 M in water, 0.300 mL, 0.300 mmol) and the vessel was heated again for 10 minutes at 120° C. Upon cooling aqueous hydrogen chloride (2M in water, 0.235 mL, 0.470 mmol) was added and the resulting mixture was diluted with 10% v/v isopropanol/chloroform (20 mL), brine (10 mL), and water (1 mL). The layers were separated and the aqueous layer was re-extracted with 10% v/v isopropanol/chloroform (10 mL). The organic layers were combined, dried over sodium sulfate, filtered, and concentrated. Lyophilization of the residue from methanol/water provided (1S,4R)-4-(5-{3-cyclopropyl-5-[(4-methylpyrimidin-2-yl)amino]phenyl}-1,3-thiazol-2-yl)-4-hydroxy-2,2-dimethylcyclohexanecarboxylic acid (34.3 mg, 0.072 mmol, 84% yield) as an off-white solid. MS ESI: [M+H]+ m/z 461.1.

Provenance & Evidence