Diisopropylamine → 2-(2-Fluoropyridin-4-yl)-1-[3-(trifluoromethyl)phenyl]ethanone

HRID 1596175Notes

Reaction equation

C(NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]1[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][N:15]=1.CON(C)[C:24](=[O:35])[C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:33])[F:32])[CH:26]=1>C1COCC1>[F:13][C:14]1[CH:19]=[C:18]([CH2:20][C:24]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:32])([F:33])[F:34])[CH:26]=2)=[O:35])[CH:17]=[CH:16][N:15]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a stirring solution of diisopropylamine (17.69 mL, 0.135 mol) in anhydrous THF (200 mL) at −78° C., under argon, was added n-butyllithium (54.0 mL, 2.5M in hexane, 0.135 mol), followed after 5 min. by a solution of 2-fluoro-4-methylpyridine (10 g, 0.090 mol) in anhydrous THF (20 mL). After stirring for 15 min. at −78° C., a solution of N-methoxy-N-methyl-3-trifluoromethylbenzamide (23.08 g, 0.099 mol) in anhydrous THF (10 mL) was added to the reaction mixture which was then stirred for 5 min., and allowed to warm to 0° C. The reaction was quenched with water (400 mL), and extracted with ethyl acetate (3×200 mL). The ethyl acetate extracts were combined, dried over anhydrous sodium sulfate, filtered, and concentrated to an oil which was chromatographed on silica gel (1 kg), eluting with 20% ethyl acetate in hexane to give 21.6 g of the title compound.

Workup

stirringwas then stirred for 5 min.
temperatureto warm to 0° C
customThe reaction was quenched with water (400 mL)
extractionextracted with ethyl acetate (3×200 mL)
dry with materialdried over anhydrous sodium sulfate
filtrationfiltered
concentrationconcentrated to an oil which
customwas chromatographed on silica gel (1 kg)
washeluting with 20% ethyl acetate in hexane

Sources & evidence

ORD record: ord-4f39549af8534704a755e8a51ea55e4a
Source dataset: uspto-grants-2001_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06291457B1

Reaction notes

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