반응 #41953

반응 방정식

hydrogen

1-Benzyl-5-(2,3-dimethylphenylhydroxymethyl)imidazole

water

HCl

→

4-[(2,3-dimethylbenzyl)]imidazole hydrochloride

용매

ethanol

반응 조건

후처리

1. 1
   여과The reaction mixture is filtered at 45±3° C.
2. 2
   세척the filter cake is washed with water (30 l)
3. 3
   workup.DISTILLATION170 l of water is distilled off under reduced pressure and 30% HCl (8 l)
4. 4
   workup.ADDITIONis added
5. 5
   기타The 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. 6
   기타The crystalline compound is collected by centrifugation
7. 7
   세척washed with toluene
8. 8
   workup.ADDITIONThe crude product and water (250 l) are charged
9. 9
   온도The solution is heated to about 50° C.
10. 10
    workup.STIRRINGstirred for 1 hour
11. 11
    온도The solution is cooled to 10° C. during 1.5 hour
12. 12
    여과The solution is filtered
13. 13
    workup.DISTILLATION180 l of water is distilled off under vacuum
14. 14
    workup.ADDITION30% HCl (20 l) is added
15. 15
    온도the solution is warmed to 60° C.
16. 16
    온도cooled to 3±3° C. during 2 hours
17. 17
    기타The solution is seeded as above until the crystallization
18. 18
    workup.STIRRINGagitated for two hours
19. 19
    기타The crystalline compound is collected by centrifugation
20. 20
    세척washed with toluene
21. 21
    기타The 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

실험 절차

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%).

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