Sodium hydride → Methyl 1-[4-(trifluoromethyl)benzyl]-1H-indole-7-carboxylate

HRID 1694381Notes

Reaction equation

[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[C:10]([O:12][CH3:13])=[O:11])[CH:3]=[CH:2]1.Br[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=1.[H-].[Na+]>CN(C=O)C>[F:23][C:22]([F:24])([F:25])[C:19]1[CH:20]=[CH:21][C:16]([CH2:15][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][C:8]=3[C:10]([O:12][CH3:13])=[O:11])[CH:3]=[CH:2]2)=[CH:17][CH:18]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Methyl 1H-indole-7-carboxylate (47.8 g, 273 mmol) and 1-(bromomethyl)-4-(trifluoromethyl)benzene (81 g, 341 mmol) were dissolved in DMF (1.3 L) at 0° C. 60% w/w NaH (12 g, 300 mmol) was added portion wise. The ice bath was removed and the mixture stirred at 0° C. for 3 hours, then overnight at RT. The reaction mixture was quenched with 3 L of NH4Cl(sat.) and the aqueous layer was extracted 3 times with 1 L of ether. The organic layers were combined, washed with water and brine. The compound was purified by flash chromatography on silica gel. 1H NMR (500 MHz, DMSO-d6): δ 8.90 (d, 1H), 7.70 (s, 1H), 7.60 (d, 2H), 7.40 (d, 1H), 7.10 (t, 1H), 7.00 (d, 2H), 6.70 (d, 1H), 5.70 (s, 2H).

Workup

customThe ice bath was removed
customovernight
customat RT
customThe reaction mixture was quenched with 3 L of NH4Cl(sat.)
extractionthe aqueous layer was extracted 3 times with 1 L of ether
washwashed with water and brine
customThe compound was purified by flash chromatography on silica gel

Sources & evidence

ORD record: ord-14382d2d81674954a6f454f1ca22531a
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08158671B2

Reaction notes

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