4-Fluoro-3-nitrobenzoic acid → 4-Fluoro-3-nitro-N,N-bis(2,2,2-trifluoroethyl)benzamide

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Reaction Steps

4-Fluoro-3-nitrobenzoic acid (2.50 g, 13.5 mmol) was refluxed in a 2:1 mixture of CH2Cl2/SOCl2 (150 mL) for 5 h. The solvent was concentrated and the residue was dissolved in CH2Cl2 (50 mL). Another CH2Cl2 solution (50 mL) of diisopropylethylamine (DIPEA) (3.50 mL, 20.3 mmol) and bis(2,2,2-trifluoroethyl)amine (4.90 g, 27.0 mmol) was then added dropwise to the cold stirring solution (0° C.) of the acid chloride. The solution was stirred at rt overnight. The solution was then washed with 5% KHSO4 solution, saturated NaHCO3 solution, brine and dried over anhydrous MgSO4. The crude product was purified by flash chromatography using 3:1/hexanes:EtOAc to afford the title product. Yield: 3.08 g (66%). 1H NMR (400 MHz, CDCl3) δ 4.17 (brs, 4H), 7.40 (t, J=8.59 Hz, 1H), 7.66 (m, 2H), 8.10 (d, J=6.84 Hz, 1H).

Provenance & Evidence