Hydrochloric Acid → Naratriptan hydrochloride

HRID 2258137Notes

Reaction equation

HRID 2258137 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 (50 L), water (35 L) and 2N hydrochloric acid (15.75 L) was hydrogenated at atmospheric pressure over 20.5 h. The catalyst was removed by filtration. The filter cake was washed with water (40 L). The filtrate was concentrated in vacuo to approximately 30 L and cooled to 18°. Ethyl acetate (70 L) was added over 1 h and the resulting suspension cooled to 5° and aged for 1 h. The product was collected by filtration, washed with ethyl acetate (20 L) and dried in vacuo at 40°-50° overnight (8.87 kg, 79.0% of theory). A portion (0.2 kg) of the solid was recrystallised from hot IMS/water (4:1) (1 L) and obtained as fine, off-white crystals (0.143 kg), 71.7% of theory).

Workup

  1. customThe catalyst was removed by filtration
  2. washThe filter cake was washed with water (40 L)
  3. concentrationThe filtrate was concentrated in vacuo to approximately 30 L
  4. temperaturecooled to 18°
  5. additionEthyl acetate (70 L) was added over 1 h
  6. temperaturethe resulting suspension cooled to 5° and aged for 1 h
  7. filtrationThe product was collected by filtration
  8. washwashed with ethyl acetate (20 L)
  9. customdried in vacuo at 40°-50° overnight (8.87 kg, 79.0% of theory)
  10. customA portion (0.2 kg) of the solid was recrystallised from hot IMS/water (4:1) (1 L)

Sources & evidence

ORD record
ord-53ba0e769b3c4f53923dca4aff485198
Source dataset
uspto-grants-1997_08
Patent number
US05659040

Reaction notes

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