反应详情

温度

50 °C

Biphenyl-2-ylcarbamic acid piperidin-4-yl ester (which may be prepared according to preparation 8 in WO 2004/074246A) (63.0 kg, 212.57 mol) was added to a stirred suspension of N-[2-chloro-4-formyl-5-(methyloxy)phenyl]-2-propenamide (which may be prepared according to Step C (Preparation 1) or C (Preparation 2)) (50.0 kg, 208.62 mol) and acetic acid (12.6 kg, 209.83 mol) in 2-methyltetrahydrofuran (430 kg) at 25° C. The mixture was then heated to 50° C. over 60 mins and held at this temperature for 2 hours. The resulting suspension was cooled to 20° C. over 90 mins and held at this temperature for 4 hours. The suspension was filtered under vacuum and the filter cake was washed with IMS (3×78.9 kg). The solid was dried in a vacuum oven at 50° C. for 10 hours to give biphenyl-2-ylcarbamic acid 1-[2-(2-chloro-4-formyl-5-methoxyphenyl-carbamoylethyl]piperidin-4-yl ester as a white solid (90.7 kg, 80.6% th).

1. temperatureThe resulting suspension was cooled to 20° C. over 90 mins
2. waitheld at this temperature for 4 hours
3. filtrationThe suspension was filtered under vacuum
4. washthe filter cake was washed with IMS (3×78.9 kg)
5. customThe solid was dried in a vacuum oven at 50° C. for 10 hours