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

HRID 862207Notes

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 solution of diisopropylamine (17.69 mL, 0.135 mole) in THF (200 mL) at -78° C., under argon, was added n-butyllithium (54.0 mL, 2.5M in hexane, 0.135 mole), followed after 5 min. by a solution of 2-fluoro-4-methylpyridine (Lancaster Synthesis Inc.) (10 g, 0.090 mole) in 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 mole) in THF (10 mL) was added. After stirring for 5 min, the reaction was allowed to warm to 0° C. and quenched by pouring into water (400 mL) and ethyl acetate (400 mL). The layers were separated, and the aqueous layer washed with ethyl acetate (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 with 20% ethyl acetate in hexane to give 21.6 g of the title compound.

Workup

stirringAfter stirring for 5 min
temperatureto warm to 0° C.
customquenched
additionby pouring into water (400 mL) and ethyl acetate (400 mL)
customThe layers were separated
washthe aqueous layer washed with ethyl acetate (200 mL)
dry with materialdried over anhydrous sodium sulfate
filtrationfiltered
concentrationconcentrated to an oil which
customwas chromatographed on silica gel with 20% ethyl acetate in hexane

Sources & evidence

ORD record: ord-ec63435d504f4ca5bbd7ab94805ca4f9
Source dataset: uspto-grants-1998_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05717100

Reaction notes

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