Sodium hydride → 6-Chloro-2'-methylspiro[benzofuran-2(3H),4'(2'H)-isoquinoline] hydrochloride

Participants

Reaction Steps

A solution of 4-(4-chloro-2-fluorobenzyl)-2-methyl-1,2,3,4-tetrahydro-4-isoquinolinol (10.0 g) in toluene (65 ml) and dimethylformamide (10 ml) is added dropwise to a suspension of sodium hydride (50%, 3.2 g), previously washed with hexane, in toluene (65 ml). After the addition is complete, the mixture is brought to reflux and dimethylformamide (35 ml) is slowly added dropwise. The reaction mixture is heated under reflux for four hours. Removal of the solvents yields an oil which is stirred in water (500 ml) and extracted with chloroform. The combined organic extracts are washed with water, saturated sodium chloride solution and dried over anhydrous magnesium sulfate. After filtering, removal of the solvent yields an oil which is dissolved in ether and converted to the product hydrochloride salt. The salt is recrystallized from ethyl acetate/methanol to yield the product as a white solid (6.8 g, 60%), mp 196°-199°. An analytical sample is twice recrystallized to yield a white solid, mp 200.5°-202° (dec.).

Provenance & Evidence