反应详情

温度

3 °C

1-Benzyl-5-(2,3-dimethylphenylhydroxymethyl)imidazole (20 kg), water (225 l), 30% HCl (20 l), ethanol (5 l) and palladium on charcoal 10% (4.4 kg) are charged. The mixture is stirred under 2.2 bar overpressure of hydrogen at 75±5° C. for 24 hours. The reaction mixture is filtered at 45±3° C. and the filter cake is washed with water (30 l). 170 l of water is distilled off under reduced pressure and 30% HCl (8 l) is added. The solution is cooled to 3±3° C. during 2 h. The solution is seeded with crystals of detomidine HCl at 40±5° C., 30±5° C., 20±5° C. and at 10±5° C., until the crystallization starts. The mixture is agitated for two hours. The crystalline compound is collected by centrifugation and washed with toluene. The crude product and water (250 l) are charged. The solution is heated to about 50° C. and stirred for 1 hour. The solution is cooled to 10° C. during 1.5 hour. The solution is filtered and 180 l of water is distilled off under vacuum. 30% HCl (20 l) is added and the solution is warmed to 60° C., and then cooled to 3±3° C. during 2 hours. The solution is seeded as above until the crystallization starts and agitated for two hours. The crystalline compound is collected by centrifugation and washed with toluene. The product is dried under vacuum at 39±5° C. for 20 hours, at 61±5° C. for 6 hours and at 85±5° C. for 16 hours. The yield is 10.5 kg (78%).

1. filtrationThe reaction mixture is filtered at 45±3° C.
2. washthe filter cake is washed with water (30 l)
3. distillation170 l of water is distilled off under reduced pressure and 30% HCl (8 l)
4. additionis added
5. customThe solution is seeded with crystals of detomidine HCl at 40±5° C., 30±5° C., 20±5° C. and at 10±5° C., until the crystallization
6. customThe crystalline compound is collected by centrifugation
7. washwashed with toluene
8. additionThe crude product and water (250 l) are charged
9. temperatureThe solution is heated to about 50° C.
10. stirringstirred for 1 hour
11. temperatureThe solution is cooled to 10° C. during 1.5 hour
12. filtrationThe solution is filtered
13. distillation180 l of water is distilled off under vacuum
14. addition30% HCl (20 l) is added
15. temperaturethe solution is warmed to 60° C.
16. temperaturecooled to 3±3° C. during 2 hours
17. customThe solution is seeded as above until the crystallization
18. stirringagitated for two hours
19. customThe crystalline compound is collected by centrifugation
20. washwashed with toluene
21. customThe product is dried under vacuum at 39±5° C. for 20 hours, at 61±5° C. for 6 hours and at 85±5° C. for 16 hours