Reaction #89584

Reaction equation

1-Bromopentane

Sodium hydride

Water

1-(1H-indol-3-yl)-2-(2-methoxyphenyl)ethanone

→

2-(2-methoxyphenyl)-1-(1-pentyl-1H-indol-3-yl)ethanone

Yield 49.0%

Solvents

dimethylformamide

Conditions

Workup

1. 1
   workup.ADDITIONafter the addition
2. 2
   workup.STIRRINGthe reaction mixture was stirred at room temperature overnight
3. 3
   Extractionthe mixture was extracted three times with ethyl acetate (3×200 ml)
4. 4
   Washwashed with water (200 ml) and brine (200 ml)
5. 5
   Dryingdried over sodium sulphate
6. 6
   Concentrationconcentrated in vacuo
7. 7
   OtherThe residue was purified by column chromatography (Biotage Isolera 4, SNAP-100 g, 5%-20% ethyl acetate hexane containing 5% dichloromethane)

Procedure

60% Sodium hydride in mineral oil (1.8 g, 45.23 mmol) was suspended in dimethylformamide (100 ml) and 1-(1H-indol-3-yl)-2-(2-methoxyphenyl)ethanone 3 (10 g, 37.70 mmol) was added portionwise at room temperature, allowing to stir further 45 min at room temperature after the addition was finished. 1-Bromopentane (7.02 ml, 56.55 mmol) was added dropwise at room temperature and the reaction mixture was stirred at room temperature overnight. Water (200 ml) was added and the mixture was extracted three times with ethyl acetate (3×200 ml). The organic fractions were combined, washed with water (200 ml) and brine (200 ml) and dried over sodium sulphate and concentrated in vacuo. The residue was purified by column chromatography (Biotage Isolera 4, SNAP-100 g, 5%-20% ethyl acetate hexane containing 5% dichloromethane) to give 6.2 g (41%) of 2-(2-methoxyphenyl)-1-(1-pentyl-1H-indol-3-yl)ethanone (JWH-250) 4 as an orange/tan solid.

Source