Benzyl Bromide → (r)-1-Benzyl-5-bromo-3-(1-methyl-2-pyrrolidinylmethyl)-1h-indole

Participants

Reaction Steps

To a stirred solution of (R)-5-bromo-3-(1-methyl-2-pyrrolidinylmethyl)-1H-indole (see Example 27, WO 92/06973) (21.44 g, 73.2 mmol) in tetrahydrofuran (110 ml) at 0° C. under a nitrogen atmosphere was added sodium hydride (60% dispersion in mineral oil, 3.51 g, 87.7 mmol) portionwise, maintaining the temperature below 5° C. Upon completion of the addition, the dark brown solution was stirred at 0-5° C. for 1 hr before benzyl bromide (10.4 ml, 87.4 mmol) was added dropwise maintaining the temperature below 5° C. The brown solution was then warmed to ambient temperature over a 1 hr period before being quenched into water (100 ml). The mixture was then extracted with ethyl acetate (3×25 ml) and the organic extracts were combined and evaporated in vacuo to yield a brown oil. This was purified by flash column chromatography (ethyl acetatehexane:diethylamine 1:1:0.1 as eluant) to give the subtitle compound (17.6 g, 63%) as a brown viscous oil.

Provenance & Evidence