Verilopam synthesis

Yield:-

Reaction Conditions:

with hydrogenchloride in tetrahydrofuran;ethanol;

Steps:

2.1 METHOD 1

METHOD 1 Preparation of 3-(4-aminophenethyl)-1,2,4,5-tetrahydro-7,8-dimethoxy-3H,3-benzazepine To a stirred suspension of lithium aluminum hydride (7.42 g, 0.1952 m, 4 molar excess) in 200 ml dry THF under N₂ at ambient temperature was added dropwise a solution of 3-(4-aminophenylacetyl)-1,2,4,5-tetrahydro-7,8-dimethoxy-3H,3-benzazepine (16.6 g, 0.0488 m) in 200 ml dry THF which was heated to obtain a solution. The mixture was stirred for 2 hrs at ambient temperature, then cooled with an ice bath and quenched with 10% NaOH (16 ml), stirred for 1 hr, then the precipitated salts removed by filtration and the solvent evaporated to afford the crude product as an off-white solid, 14.2 g (89%). This material was purified by chromatography on alumina saturated with ammonia, eluding with 10% ether/CHCl₃ and afforded 11.9 g (75%) pure product. Alternatively, the free base may be purified by crystallization from cyclohexane, or better, from 95% ethanol, the latter of which gives a white solid, m.p. 156.5°-157° C. The bis-hydrochloride salt is prepared by acidifying a 2/1 MeOH/THF solution of the free base with HCl gas, followed by charcoal treatment and crystallization and may be recrystallized from absolute ethanol or 95% ethanol and ether. The solid product obtained melts at 233°-235° C. dec. and is hydrated with water.

References:

US4282146,1981,A