Succinic Acid → Batefenterol Succinate

Participants

Reaction Steps

Biphenyl-2-ylcarbamic acid 1-[2-(2-chloro-4-{[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]methyl}-5-methoxyphenylcarbamoyl)-ethyl]piperidin-4-yl ester (prepared as in Preparation 1) (200 mg) was suspended in methanol (1.5 ml) at ˜70° C. A first portion (100 μl) of succinic acid in methanol was added, from a total of succinic acid (67 mg, 2.1 equiv) in methanol (0.5 ml), and the temperature reduced to 50° C. The remaining succinic acid in methanol was added in four further portions (100 μl) over approximately 5 hours, with further methanol (1 ml) added after 3 h, to replace lost solvent. After a further 30 min. The resulting slurry was temperature cycled between 0° C. and 40° C. over 5 days. The resulting solid was isolated by filtration, washed with THF, dried on filter paper and then in a vacuum oven, to provide the title compound as a crystalline solid (148 mg).

Provenance & Evidence