Methanesulfonic Acid → Eletriptan

HRID 1901577Notes

Reaction equation

HRID 1901577 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.CS(O)(=O)=O.[H][H]>CC(C)=O.[Pd]>[C:1]1([S:7]([CH2:10][CH2:11][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:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 3

HCID 6395Methanesulfonic AcidHCID 540753983-(((2R)-1-Methyl-2-pyrrolidinyl)methyl)-5-(2-(phenylsulfonyl)ethenyl)-1H-indoleHCID 178418361HCID 178418361, compound

Product 1

HCID 77993EletriptanYield 73.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 180AcetoneSolvent

Procedure

A stirred solution of (R)-5-(2-benzenesulfonylethenyl)-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole (34.0 g) in acetone (200 mL) was treated with methanesulfonic acid (8.5871 g) then 5% palladium on carbon (50% wet) (34.0 g) added and the mixture exposed to hydrogen (50 psi) at ambient temperature. When conversion was judged to be complete the mixture was filtered (washing with acetone-85 mL-and mixed acetone/water-81 mL/4 mL). The combined filtrate and washings were diluted with water (800 mL) and the pH adjusted (with stirring) to about 11 by addition of 40% aqueous sodium hydroxide. After granulation of the precipitate the solids were collected by filtration to give the title compound (25.08 g) as that produced in Example 32).

Workup

  1. filtrationwas filtered
  2. wash(washing with acetone-85 mL-and mixed acetone/water-81 mL/4 mL)
  3. additionThe combined filtrate and washings were diluted with water (800 mL)
  4. additionby addition of 40% aqueous sodium hydroxide
  5. filtrationAfter granulation of the precipitate the solids were collected by filtration

Sources & evidence

ORD record
ord-0693e8efe97a4e5882225f94ecdd37b2
Source dataset
uspto-grants-1996_11
Patent number
US05578612

Reaction notes

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