Hydrochloric Acid → Naratriptan hydrochloride

HRID 1957727Notes

Reaction equation

HRID 1957727 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.O.[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

6

Reactant 2

HCID 313Hydrochloric AcidHCID 14392648HCID 14392648, compound

Product 1

HCID 60875Naratriptan hydrochloride

Reagents, catalysts & solvents 3

HCID 5083724Palladium monoxideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of (E)-N-methyl-2-[3-(1,2,3,6-tetrahydro-1-methyl-4-pyridinyl)-1H-indol-5-yl]ethenesulphonamide (10 kg) and 10% palladium oxide on charcoal (10 kg, 50% wet paste, added as two charges) in DMF (50L), water (20L) and 2N hydrochloric acid (15L) was hydrogenated at atmospheric pressure over 18.5 hr. The catalyst was removed by filtration. The filter cake was washed with water (20L). The filtrate was concentrated in vacuo to approximately 30L and cooled to 20°. Ethyl acetate (70L) was added over 1 hr and the resulting suspension cooled to 50 and aged for 30 min. The product was collected by filtration, washed with ethyl acetate (20L) and dried in vacuo at 40°-50° overnight (9.34 kg, 81.6% of theory). A portion (2.0 kg) of the solid was recrystallised from hot water (6.0L) and obtained as white crystals (1.40 kg, 70% of theory).

Workup

  1. customThe catalyst was removed by filtration
  2. washThe filter cake was washed with water (20L)
  3. concentrationThe filtrate was concentrated in vacuo to approximately 30L
  4. temperaturecooled to 20°
  5. additionEthyl acetate (70L) was added over 1 hr
  6. temperaturethe resulting suspension cooled to 50
  7. waitaged for 30 min
  8. filtrationThe product was collected by filtration
  9. washwashed with ethyl acetate (20L)
  10. customdried in vacuo at 40°-50° overnight (9.34 kg, 81.6% of theory)
  11. customA portion (2.0 kg) of the solid was recrystallised from hot water (6.0L)
  12. customobtained as white crystals (1.40 kg, 70% of theory)

Sources & evidence

ORD record
ord-6493fbe2ed914fd7a4268d36c6778311
Source dataset
uspto-grants-1998_07
Patent number
US05786473

Reaction notes

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