Hydrochloric Acid → Paliperidone

HRID 1429763Notes

Reaction equation

HRID 1429763 reaction equation
Cl.CCCCCCCCCCCCCCCC(O)=O.[CH3:20][C:21]1[N:31]=[C:30]2[N:25]([CH2:26][CH2:27][CH2:28][CH:29]2[OH:32])[C:23](=[O:24])[C:22]=1[CH2:33][CH2:34][N:35]1[CH2:40][CH2:39][CH:38]([C:41]2[C:42]3[CH:43]=[CH:44][C:45]([F:50])=[CH:46][C:47]=3[O:48][N:49]=2)[CH2:37][CH2:36]1>>[CH3:20][C:21]1[N:31]=[C:30]2[N:25]([CH2:26][CH2:27][CH2:28][CH:29]2[OH:32])[C:23](=[O:24])[C:22]=1[CH2:33][CH2:34][N:35]1[CH2:40][CH2:39][CH:38]([C:41]2[C:42]3[CH:43]=[CH:44][C:45]([F:50])=[CH:46][C:47]=3[O:48][N:49]=2)[CH2:37][CH2:36]1

Participants

3

Reactant 2

HCID 313Hydrochloric AcidHCID 18542499HCID 18542499, compound2×

Product 1

HCID 115237Paliperidone

Conditions

Temperature
77.5 °C

Procedure

A mixture of dilute hydrochloric acid and paliperidone palmitate heated to 75-80° C. and the reaction was maintained for 2 hours at 75-80° C., monitored the reaction by HPLC for absence of paliperidone palmitate and cooled the reaction mass to 25-30° C. The reaction mass was washed with methylene chloride, added a mixture of methylene chloride and methanol to aqueous layer, cooled the contents to 10° C., adjusted pH 10-12 with 20% sodium hydroxide in water solution at 10-30° C., extracted the compound into methylene chloride at basic condition and washed the methylene chloride layer with purified water and the separated methylene chloride layer treated with activated carbon, filtered the carbon through hyflow bed, washed with methylene chloride, the methylene chloride was distilled off completely under vacuum and added Isopropyl alcohol, heated the contents to reflux temperature and slowly cooled to 25-30° C., stirred for 1 hour at the same temperature, filtered the isolated compound, washed the wet compound with Isopropyl alcohol and dried under vacuum at 55-60° C. to get pure paliperidone.

Workup

  1. temperaturethe reaction was maintained for 2 hours at 75-80° C.
  2. temperaturecooled the reaction mass to 25-30° C
  3. washThe reaction mass was washed with methylene chloride
  4. additionadded
  5. additiona mixture of methylene chloride and methanol to aqueous layer
  6. temperaturecooled the contents to 10° C.
  7. extractionadjusted pH 10-12 with 20% sodium hydroxide in water solution at 10-30° C., extracted the compound into methylene chloride at basic condition
  8. washwashed the methylene chloride layer with purified water
  9. additionthe separated methylene chloride layer treated with activated carbon
  10. filtrationfiltered the carbon through hyflow bed
  11. washwashed with methylene chloride
  12. distillationthe methylene chloride was distilled off completely under vacuum
  13. additionadded Isopropyl alcohol
  14. temperatureheated the contents
  15. temperatureto reflux temperature
  16. temperatureslowly cooled to 25-30° C.
  17. filtrationfiltered the isolated compound
  18. washwashed the wet compound with Isopropyl alcohol
  19. customdried under vacuum at 55-60° C.

Sources & evidence

ORD record
ord-cd39481bc9d74a75a47493b7d7b561d2
Source dataset
uspto-grants-2015_01
Patent number
US08940749B2

Reaction notes

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