反应详情

温度

90 °C

A stirred mixture of pyridine (15.5 kg) and piperidine (0.72 kg) were heated to 90° C. Malonic acid (17.6 kg) was added, followed by slow addition, over 50 minutes, of 3,4-difluorobenzaldehyde (12.0 kg). The reaction mixture was stirred at 90° C. for a further 4 hours and 36 minutes. Water (58.5 kg) was added and 32 litres of the pyridine/water mixture then was distilled out of the reactor under reduced pressure. The reaction mixture was acidified to pH 1 with 37% hydrochloric acid (6.4 kg) over a 40 minute period, then cooled to 25° C. with strong stirring. The solids were collected by filtration, washed twice with 1% hydrochloric acid (34.8 L per wash), once with water (61 L) and then deliquored thoroughly in the filter. The product was then dried under vacuum at 40° C. for 24 hours and 40 minutes, affording 13.7 kg of the crystalline product.

1. distillation32 litres of the pyridine/water mixture then was distilled out of the reactor under reduced pressure
2. waitThe reaction mixture was acidified to pH 1 with 37% hydrochloric acid (6.4 kg) over a 40 minute period
3. temperaturecooled to 25° C. with strong stirring
4. filtrationThe solids were collected by filtration
5. washwashed twice with 1% hydrochloric acid (34.8 L per wash), once with water (61 L)
6. customThe product was then dried under vacuum at 40° C. for 24 hours and 40 minutes