Hydrochloric Acid → Naratriptan hydrochloride

HRID 2258138Notes

Reaction equation

HRID 2258138 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-(1,2,3,6-tetrahydro-1-methyl-4-pyridinyl)-1H-indol-5-yl]ethenesulphonamide (8.6 kg) and 10% palladium oxide on charcoal (2.58 kg, 50% wet pastel in DMF (86 L) and 2 N 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; 30 L). 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 (2×30 L). The filtrates from two hydrogenations could be combined for work-up. Thus the combined solutions were treated with 2M hydrochloric acid (1.72 L) then concentrated in vacuo to approximately 52 L. Ethyl acetate (120 L) was added, the resulting suspension cooled to 3° and aged for 1 h. The product was collected by filtration, washed with ethyl acetate (2×26 L) and dried in vacuo at 40°-50° overnight (15.96 kg, 83% of theory). Recrystallisation from hot IMS/water (7:1; 206 L) 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; 30 L)
  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 (2×30 L)
  6. additionThus the combined solutions were treated with 2M hydrochloric acid (1.72 L)
  7. concentrationthen concentrated in vacuo to approximately 52 L
  8. additionEthyl acetate (120 L) was added
  9. temperaturethe resulting suspension cooled to 3° and aged for 1 h
  10. filtrationThe product was collected by filtration
  11. washwashed with ethyl acetate (2×26 L)
  12. customdried in vacuo at 40°-50° overnight (15.96 kg, 83% of theory)
  13. customRecrystallisation from hot IMS/water (7:1; 206 L)
  14. customgave fine

Sources & evidence

ORD record
ord-fab15113bcfd473e83d25d27d1d34798
Source dataset
uspto-grants-1997_08
Patent number
US05659040

Reaction notes

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