Cesium fluoride → Methyl 4-(5-(2,2,2-trifluoro-1-hydroxyethyl)thiophen-2-yl)butanoate

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Reaction Steps

CsF (70 mg, 0.47 mmol) was added to a solution of methyl 4-(5-formylthiophen-2-yl)butanoate (1.0 g, 4.71 mmol) in dry 1,2-dimethoxyethane (5 MI) at 0° C., followed by trifluoromethyl trimethylsilane (0.8 MI, 5.65 mmol) dropwise. The reaction mixture was stirred at room temperature for 4 h, quenched with 3N HCl, and stirred for further 30 min. The crude product was extracted with EtOAc. The combined extracts were washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica 60-120 mesh, eluant 10% EtOAc in petroleum ether) to get methyl 4-(5-(2,2,2-trifluoro-1-hydroxyethyl)thiophen-2-yl)butanoate (0.63 g, yield 47%) as yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.02-7.01 (d, J=3.5 Hz, 1H), 6.74-6.73 (m, 1H), 5.23-5.17 (m, 1H), 3.68 (s, 3H), 2.88-2.84 (t, J=7.5 Hz, 2H), 2.81-2.80 (d, J=5.3 Hz, 1H), 2.40-2.36 (t, J=7.5 Hz, 2H), 2.05-1.97 (m, 2H).

Provenance & Evidence