Water → Jwh 250

HRID 61306Notes

Reaction equation

HRID 61306 reaction equation
[H-].[Na+].[NH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12](=[O:22])[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[O:20][CH3:21])=[CH:4]1.Br[CH2:24][CH2:25][CH2:26][CH2:27][CH3:28].O>CN(C)C=O>[CH3:21][O:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[CH2:13][C:12]([C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[N:3]([CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[CH:4]=1)=[O:22]

Participants

6

Reactant 4

HCID 962WaterHCID 80571-BromopentaneHCID 24758Sodium hydrideHCID 433392871-(1H-Indol-3-yl)-2-(2-methoxyphenyl)ethanone

Product 1

HCID 44397540Jwh 250Yield 49%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

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.

Workup

  1. additionafter the addition
  2. stirringthe reaction mixture was stirred at room temperature overnight
  3. extractionthe mixture was extracted three times with ethyl acetate (3×200 ml)
  4. washwashed with water (200 ml) and brine (200 ml)
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (Biotage Isolera 4, SNAP-100 g, 5%-20% ethyl acetate hexane containing 5% dichloromethane)

Sources & evidence

ORD record
ord-400ac1010ebe48afbdd94ee843771965
Source dataset
uspto-grants-2016_09
Patent number
US09441033B2

Reaction notes

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