Manufacturing Process
A mixture of the appropriate phenyl vinyl sulfone, tri-o-tolylphosphine,
palladium (II) acetate, triethlamine and (R)-5-bromo-3-(Nmethylpyrrolidinylmethyl)-1H-indole in anhydrous acetonitrle was heated at
reflux under nitrogen. The resultant reaction mixture was evaporated under
reduced pressure, and the residue was column chromatographed using silica
gel and elution with methylene chloride/absolute ethanol/ammonia to afford
the (R )-5-trans-(2-phenylsulfonylethenyl)-3-(N-methylpyrrolidin-2-ylmethyl)-
1H-indole.
A solution of (R)-5-trans-(2-phenylsulfonylethenyl)-3-(N-methylpyrrolidin-2-
ylmethyl)-1H-indole and 10% Pd/C in ethanolic hydrogen chloride (prepared
from absolute ethanol and acetyl chloride and N,N-dimethylformamide was
shaken under a hydrogen atmosphere at room temperature). The resultant
reaction mixture was filtered through diatomaceous earth (Celite trademark),
washed with absolute ethanol, and the combined filtrates were evaporated
under reduced pressure. The residue was partitioned between ethyl acetate
and water. The organic phase was separated, washed with water, brine, dried(Na2SO4), and evaporated under reduced pressure to afford a oil product.
Column chromatography of this product using silica gel and elution with
methylene chloride/absolute ethanol/ammonia afforded the appropriate (R)-5-
(2-phenylsulfonylethyl)-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole.
The salt eletriptan hydrobromide may be produced by reaction of the (R)-5-
(2-phenylsulfonylethyl)-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole with
hydrobromic acid.
