Hydrochloric Acid → Naratriptan hydrochloride

HRID 1957730Notes

Reaction equation

HRID 1957730 reaction equation
[CH3:1][NH:2][S:3](/[CH:6]=[CH:7]/[C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][CH:12]=[C:11]2[C:17]1[CH2:18][CH2:19][N:20]([CH3:23])[CH2:21][CH:22]=1)(=[O:5])=[O:4].[ClH:24]>CN(C=O)C.[Pd]=O>[ClH:24].[CH3:1][NH:2][S:3]([CH2:6][CH2:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][CH:12]=[C:11]2[CH:17]1[CH2:18][CH2:19][N:20]([CH3:23])[CH2:21][CH2:22]1)(=[O:4])=[O:5]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 14392648HCID 14392648, compound

Product 1

HCID 60875Naratriptan hydrochloride

Reagents, catalysts & solvents 2

HCID 5083724Palladium monoxideCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of (E)-N-methyl-2-[3-(1,2,3,6tetrahydro-1-methyl-4-pyridinyl)-1H-indol-5-yl]ethenesulphonamide (8.6 kg) and 10% palladium oxide on charcoal (2.58 kg, 50% wet paste) in DMF (86L) and 2N hydrochloric acid (12.3 kg) was hydrogenated at atmospheric pressure over 21 h. The catalyst was removed by filtration. The filter cake was washed with DMF/water (1:1; 30L). The combined washings and filtrate were then treated with decolourising charcoal (0.86 kg) at 75°-80° for 2 h. The suspension was filtered and the residue washed with DMF/water (2×30L). The filtrates from two hydrogenations could be combined for work-up. Thus the combined solutions were treated with 2M hydrochloric acid (1.72L) then concentrated in vacuo to approximately 52L. Ethyl acetate (120L) was added, the resulting suspension cooled to 30 and aged for 1 h. The product was collected by filtration, washed with ethyl acetate (2×26L) and dried in vacuo at 40°-50° overnight (15.96 kg, 83% of theory). Recrystallisation from hot IMS/water (7:1; 206L) gave fine, off-white crystals (13.02 kg, 84% of theory).

Workup

  1. customThe catalyst was removed by filtration
  2. washThe filter cake was washed with DMF/water (1:1; 30L)
  3. additionThe combined washings and filtrate were then treated with decolourising charcoal (0.86 kg) at 75°-80° for 2 h
  4. filtrationThe suspension was filtered
  5. washthe residue washed with DMF/water (2×30L)
  6. additionThus the combined solutions were treated with 2M hydrochloric acid (1.72L)
  7. concentrationthen concentrated in vacuo to approximately 52L
  8. additionEthyl acetate (120L) was added
  9. temperaturethe resulting suspension cooled to 30
  10. waitaged for 1 h
  11. filtrationThe product was collected by filtration
  12. washwashed with ethyl acetate (2×26L)
  13. customdried in vacuo at 40°-50° overnight (15.96 kg, 83% of theory)
  14. customRecrystallisation from hot IMS/water (7:1; 206L)
  15. customgave fine

Sources & evidence

ORD record
ord-c9b57df1de2a4b60b328698294acfaf2
Source dataset
uspto-grants-1998_07
Patent number
US05786473

Reaction notes

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