Dimethylformamide → 6-(trifluoromethyl)-1H-indole-4-carbaldehyde

HRID 913900Notes

Reaction equation

Br[C:2]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.C([Li])CCC.CN(C)[CH:22]=[O:23]>O1CCCC1.[Cl-].[Na+].O>[F:12][C:11]([F:14])([F:13])[C:9]1[CH:10]=[C:2]([CH:22]=[O:23])[C:3]2[CH:4]=[CH:5][NH:6][C:7]=2[CH:8]=1

Participants

Conditions

Temperature: -78 °C

Procedure

A solution of 4-bromo-6-(trifluoromethyl)-1H-indole (5.23 g, 19.81 mmol) in tetrahydrofuran (20 ml) was cooled to −78 ° C. and treated slowly with n-butyllithium (1.6 M solution in hexanes, 39.6 ml, 63.4 mmol). The solution was stirred for 15 min at −78 ° C., and then treated with dimethylformamide (7.67 ml, 99 mmol), and stirred for 30 minutes more, allowing the reaction to warm to ambient temperature. The resulting solution was poured into brine and extracted with ethyl acetate. The pooled organics were dried over sodium sulfate and concentrated to give an amber oil. Column chromatography (ethyl acetate/hexanes gradient elution) afforded 1.17 g, (32%). 1H-NMR (CDCl3, 500 MHz) δ ppm 10.28 (s, 1H), 8.72 (br s, 1H), 7.93 (s, 1H), 7.88 (s, 1H), 7.58 (s, 1H), 7.42 (s, 1H). Mass spec.: 214.14 (MH)+.

Workup

stirringstirred for 30 minutes more
customthe reaction
temperatureto warm to ambient temperature
extractionextracted with ethyl acetate
dry with materialThe pooled organics were dried over sodium sulfate
concentrationconcentrated
customto give an amber oil
washColumn chromatography (ethyl acetate/hexanes gradient elution)
customafforded 1.17 g, (32%)

Sources & evidence

ORD record: ord-f6337f00924e41c691fd751eb480d7de
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08026257B2

Reaction notes

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