反应详情

温度

70 °C

Ethanol (14 ml) was added to 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 (1.5 g) and heated at ˜70° C. for 1 h. The temperature was then lowered to 50° C. and succinic acid (251.25 mg, 1.05 equiv) in ethanol (2 ml) was added portionwise over approximately 4 hours. After all the acid was added, water (2.25 ml) was added, followed by a further 30 min at 50° C. The reaction was then temperature cycled between 0° C. and 40° C. over 3 days. The resulting white solid was isolated by filtration, washed with ethanol and dried in a vacuum oven at ambient temperature, to provide the title compound as a crystalline solid (727 mg).

1. customwas then lowered to 50° C.
2. additionAfter all the acid was added
3. waittemperature cycled between 0° C. and 40° C. over 3 days
4. customThe resulting white solid was isolated by filtration
5. washwashed with ethanol
6. customdried in a vacuum oven at ambient temperature