Hydrochloric Acid → HCID 178424857, compound

HRID 13675Notes

Reaction equation

HRID 13675 reaction equation
C([N:8]1[C:12]([CH:13]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[C:16]=2[CH3:22])O)=[CH:11][N:10]=[CH:9]1)C1C=CC=CC=1.O.[ClH:24].[H][H]>[Pd].C(O)C>[ClH:24].[CH3:22][C:16]1[C:17]([CH3:21])=[CH:18][CH:19]=[CH:20][C:15]=1[CH2:13][C:12]1[N:8]=[CH:9][NH:10][CH:11]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 17748062(1-Benzyl-1H-imidazol-5-yl)(2,3-dimethylphenyl)methanolHCID 178418361HCID 178418361, compound

Product 1

HCID 178424857HCID 178424857, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
3 °C

Procedure

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%).

Workup

  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

Sources & evidence

ORD record
ord-d18d83dfb0f8435faef31592c7f25ad1
Source dataset
uspto-grants-2010_06
Patent number
US07728147B2

Reaction notes

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