(Trifluoromethyl)trimethylsilane → tert-Butyl 2-chloro-6-(2,2,2-trifluoro-1-hydroxyethyl)isonicotinate

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Reaction Conditions

Reaction Steps

To a solution of tert-butyl 2-chloro-6-formylisonicotinate (1.5 g, 6.2 mmol) in THF (40 mL) were added (trifluoromethyl)trimethylsilane (1.49 mL, 4.31 mmol) and ground 4 A° molecular sieves. The mixture was cooled to 0° C. and TBAP (1.0 M in THF; 1.86 mL, 1.86 mmol) was added dropwise. The mixture was warmed to ambient temperature. After 30 min, additional (trifluoromethyl)trimethylsilane (0.5 mL, 1.44 mmol), TBAP (1.0 M in THF; 0.62 mL, 0.62 mmol) and ground 4 A° molecular sieves were added. After 30 min, the mixture was filtered with Celite. Aqueous 1 N HCl was added to the filtrate and the filtrate was extracted with ethyl acetate (3×). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% hexanes→95% hexanes/ethyl acetate) gave the title compound (1.4 g). MS 312.2 (M+1).

Provenance & Evidence