Acetone → Eletriptan

HRID 584852Notes

Reaction equation

HRID 584852 reaction equation
[C:1]1([S:7]([CH:10]=[CH:11][C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[NH:17][CH:16]=[C:15]3[CH2:21][C@H:22]2[CH2:26][CH2:25][CH2:24][N:23]2[CH3:27])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC(C)=O.CS(O)(=O)=O>[Pd].O>[CH3:27][N:23]1[CH2:24][CH2:25][CH2:26][C@@H:22]1[CH2:21][C:15]1[C:14]2[C:18](=[CH:19][CH:20]=[C:12]([CH2:11][CH2:10][S:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)(=[O:8])=[O:9])[CH:13]=2)[NH:17][CH:16]=1

Participants

6

Reactant 3

HCID 180Acetone2×HCID 6395Methanesulfonic AcidHCID 540753983-(((2R)-1-Methyl-2-pyrrolidinyl)methyl)-5-(2-(phenylsulfonyl)ethenyl)-1H-indole

Product 1

HCID 77993EletriptanYield 109.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 962WaterSolvent2×

Procedure

(R)-5-(2-Phenylsulphonylethenyl)-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole (200 kg dry equivalent) and acetone (1186.5 kg) were charged to a dry, glass lined vessel. De-ionised water (300 kg), further acetone (237 kg), methanesulphonic acid (55 kg) and a slurry of palladium on carbon (22.4 kg dry equivalent) in de-ionised water (200 kg) were added and the mixture was hydrogenated under an atmosphere of hydrogen gas. The reaction slurry was filtered to remove the catalyst. De-ionised water (1300 kg) and 48% aqueous sodium hydroxide solution (60 kg) were added to precipitate the product, which was isolated by filtration and washed with a mix of de-ionised water (210 kg), acetone (83 kg) and further de-ionised water (710 kg) to yield 3-{[1-methylpyrrolidin-2(R)-yl]methyl}-5-(2-phenylsulphonylethyl)-1H-indole (220 kg wet, 157.65 kg when dry, 78.41%).

Workup

  1. filtrationThe reaction slurry was filtered
  2. customto remove the catalyst
  3. additionDe-ionised water (1300 kg) and 48% aqueous sodium hydroxide solution (60 kg) were added
  4. customto precipitate the product
  5. customwhich was isolated by filtration
  6. washwashed with
  7. additiona mix of de-ionised water (210 kg), acetone (83 kg) and further de-ionised water (710 kg)

Sources & evidence

ORD record
ord-9745757e16744894a127a6ffeb3b509c
Source dataset
uspto-grants-2005_08
Patent number
US06927296B2

Reaction notes

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