反应详情

温度

50 °C

1-[2-(4-Benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea (1.01 kg, 1 equivalent) is dissolved in ethanol (3.05 kg) under stirring (200±20 rpm) and the mixture is heated at 50° C. Aqueous sulfuric acid (1M, 1.1 equivalents) is added during 20 minutes. The crystallization is initiated by a wet seed of Example 1 (1%) as described below. The obtained mixture is maintained at 50° C. for about 15 minutes, then it is cooled to 0° C. with a cooling rate of 15° C./h and maintained at this temperature for least 1 hour before filtration and washing with aqueous ethanol (50% W/W, 3 kg). The solid is dried in a conductive agitated dryer at a temperature of 35±3° C. under a wet stream of nitrogen (45±5% RH), optionally under stirring (max. 70 rpm) in case the cake humidity is below 25%, to provide the title compound with a purity of 99.8% with a yield of approximately 94%.

1. customThe crystallization
2. temperatureThe obtained mixture is maintained at 50° C. for about 15 minutes
3. temperatureit is cooled to 0° C. with a cooling rate of 15° C./h
4. temperaturemaintained at this temperature for least 1 hour before filtration
5. washwashing with aqueous ethanol (50% W/W, 3 kg)
6. customThe solid is dried in a conductive agitated dryer at a temperature of 35±3° C. under a wet stream of nitrogen (45±5% RH)
7. stirringoptionally under stirring (max. 70 rpm) in case the cake humidity is below 25%