Hydrochloric Acid → Serazapine Hydrochloride

HRID 648925Notes

Reaction equation

HRID 648925 reaction equation
[CH3:1][N:2]1[CH2:27][CH2:26][N:5]2[C:6]3[CH:25]=[CH:24][CH:23]=[CH:22][C:7]=3[CH2:8][N:9]3[C:17]4[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=4[C:11]([C:18]([O:20][CH3:21])=[O:19])=[C:10]3[CH:4]2[CH2:3]1.[ClH:28]>CO>[ClH:28].[CH3:1][N:2]1[CH2:27][CH2:26][N:5]2[C:6]3[CH:25]=[CH:24][CH:23]=[CH:22][C:7]=3[CH2:8][N:9]3[C:17]4[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=4[C:11]([C:18]([O:20][CH3:21])=[O:19])=[C:10]3[CH:4]2[CH2:3]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 60677Serazapine

Product 1

HCID 60676Serazapine Hydrochloride

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

Methanol (20 L) and 2.37 kg of methyl 1,3,4,16b-tetrahydro-2-methyl-2H,10H-indolo[2,1-c]pyrazino[1,2-a][1,4]benzodiazepine-16-carboxylate are combined, heated to reflux, and the mixture is treated with a solution of hydrogen chloride in methanol (7.6N, 870 ml). The reaction mixture is maintained at reflux for 10 minutes and then is allowed to cool gradually to room temperature while stirring overnight. The suspension is filtered and the solid hydrochloride is washed with methanol (2×500 ml) and dried (18 hours, 80°/0.1 mm Hg). The obtained compound is added to boiling water (31 L) and the mixture is stirred at reflux until solution is complete (20 minutes). Heating is then discontinued and the mixture is stirred overnight at 15°, cooled to 5°, filtered and the collected solid is washed with water (1 L). The product is dried (6 hours, 80°/3 mm Hg; 30 hours, 100°/0.1 mm Hg), passed through a 40 mesh screening and dried further (15 hours, 110°/0.1 mm Hg) to give methyl 1,3,4,16b-tetrahydro-2-methyl-2H,10H-indolo[2,1-c]pyrazino[1,2-a][1,4]benzodiazepine-16-carboxylate hydrochloride, mp 275°-277°.

Workup

  1. temperatureheated
  2. temperatureto reflux
  3. temperatureThe reaction mixture is maintained
  4. temperatureat reflux for 10 minutes
  5. filtrationThe suspension is filtered
  6. washthe solid hydrochloride is washed with methanol (2×500 ml)
  7. customdried (18 hours, 80°/0.1 mm Hg)
  8. additionThe obtained compound is added
  9. stirringthe mixture is stirred
  10. temperatureat reflux until solution
  11. custom(20 minutes)
  12. temperatureHeating
  13. stirringthe mixture is stirred overnight at 15°
  14. temperaturecooled to 5°
  15. filtrationfiltered
  16. washthe collected solid is washed with water (1 L)
  17. customThe product is dried (6 hours, 80°/3 mm Hg; 30 hours, 100°/0.1 mm Hg)
  18. customdried further (15 hours, 110°/0.1 mm Hg)

Sources & evidence

ORD record
ord-c705eb983e604bb9b8aa1a07bead8664
Source dataset
uspto-grants-1988_04
Patent number
US04737496

Reaction notes

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