Water → 1-[6-Chloro-1-(3,5-difluoro-benzyl)-1H-indol-3-yl]-2,2,2-trifluoro-ethanone

HRID 1097828Notes

Reaction equation

[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[F:23][C:24]1[CH:25]=[C:26]([CH:29]=[C:30]([F:32])[CH:31]=1)[CH2:27]Br.O>C(#N)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11](=[O:16])[C:12]([F:13])([F:14])[F:15])=[CH:7][N:8]2[CH2:27][C:26]2[CH:25]=[C:24]([F:23])[CH:31]=[C:30]([F:32])[CH:29]=2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 2.0 g (9.4 mmol) 1-(6-chloro-1H-indol-3-yl)-2,2,2-trifluoro-ethanone, 4.59 g (14.1 mmol) cesium carbonate and 2.14 g (10.4 mmol) 3,5-difluorobenzyl bromide in 90 ml acetonitrile was heated at 80° C. for 3 h. After cooling to room temperature addition of 150 ml water was followed by extraction with three 150-ml portions of tert-butyl methyl ether. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was triturated in 30 ml hot cyclohexane. Filtration gave 2.2 g (64%) of the crude title compound as light brown solid.

Workup

temperatureAfter cooling to room temperature
extractionwas followed by extraction with three 150-ml portions of tert-butyl methyl ether
dry with materialThe combined organic layers were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was triturated in 30 ml hot cyclohexane
filtrationFiltration

Sources & evidence

ORD record: ord-17c80053c20a4c62b47e0e2b98822d46
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08143281B2

Reaction notes

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