Methane → Naratriptan hydrochloride

HRID 1957728Notes

Reaction equation

HRID 1957728 reaction equation
[ClH:1].[CH3:2][NH:3][S:4](/[CH:7]=[CH:8]/[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[C:18]1[CH2:19][CH2:20][N:21]([CH3:24])[CH2:22][CH:23]=1)(=[O:6])=[O:5].C>CN(C=O)C.CO.[Pd]=O>[ClH:1].[CH3:2][NH:3][S:4]([CH2:7][CH2:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[CH:18]1[CH2:19][CH2:20][N:21]([CH3:24])[CH2:22][CH2:23]1)(=[O:5])=[O:6]

Participants

6

Reactant 2

HCID 297MethaneHCID 19068424HCID 19068424, compound

Product 1

HCID 60875Naratriptan hydrochloride

Reagents, catalysts & solvents 3

HCID 5083724Palladium monoxideCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×

Procedure

A mixture of (E)-N-methyl-2-[3-(1,2,3,6-tetrahydro-1-methyl-4-pyridinyl)-1H-indol-5-yl]ethenesulphonamide hydrochloride (500 g) and 10% palladium oxide on charcoal (50% wet paste, 700g added as three charges) in DMF (3L), water (3L) and methanol (1.5L) was hydrogenated at atmospheric pressure over 24 hr. The suspension was filtered and the filter cake washed with water (500 mL). The filtrate was concentrated to approximately 2L by distillation in vacuo. Ethyl acetate (5L) was added over 10 mins and the mixture cooled to 5°. The product was filtered off, washed with ethyl acetate (1L) and dried in vacuo at 45° overnight (453 g, 90.1% of theory). Recrystallisation from hot water (1.36L) afforded white crystals (324.0 g, 71.2% of theory).

Workup

  1. filtrationThe suspension was filtered
  2. washthe filter cake washed with water (500 mL)
  3. concentrationThe filtrate was concentrated to approximately 2L by distillation in vacuo
  4. additionEthyl acetate (5L) was added over 10 mins
  5. temperaturethe mixture cooled to 5°
  6. filtrationThe product was filtered off
  7. washwashed with ethyl acetate (1L)
  8. customdried in vacuo at 45° overnight (453 g, 90.1% of theory)
  9. customRecrystallisation from hot water (1.36L)
  10. customafforded white crystals (324.0 g, 71.2% of theory)

Sources & evidence

ORD record
ord-14efadfcfbf24dc8b942555aec457259
Source dataset
uspto-grants-1998_07
Patent number
US05786473

Reaction notes

Loading…