Dimethylformamide → 2-Hydroxy-3-(trifluoromethyl)benzaldehyde

Participants

Reaction Conditions

Reaction Steps

A n-butyl lithium-1.58M n-hexane solution (65.9 ml, 104 mmol) was added dropwise to a solution of 2-[2-(trifluoromethyl)phenoxy]tetrahydro-2H-pyrane (21.4 g, 86.8 mmol) which was synthesized according to the method described in literature (Miller, J. A. et al., J. Org. Chem. 1993, vol. 58, pp. 2637-2639) and N,N,N′,N′-tetramethylethylenediamine (15.7 ml, 104 mmol) in diethyl ether (230 ml) at −20° C. over 10 minutes. After the reaction mixture was stirred at −20° C. for 30 minutes, it was further stirred at room temperature for 40 minutes. After the reaction mixture was cooled to −30° C. and N,N-dimethylformamide (13.5 ml, 174 mmol) was added thereto, the mixture was further stirred at room temperature for 1 hour. After the reaction mixture was carefully poured into cooled water and the mixture was extracted with ethyl acetate (three times), the organic layer was successively washed with 1N hydrochloric acid, a 5% aqueous sodium hydrogencarbonate solution, water (twice) and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate. The residue obtained by removing the solvent under reduced pressure was purified by silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=20/1-10/1). The obtained 2-(tetrahydro-2H-pyran-2-yloxy)-3-(trifluoromethyl)benzaldehyde as a pale yellow oil was left to stand at room temperature overnight to give 2-hydroxy-3-(trifluoromethyl)benzaldehyde as a pale yellow solid (31.7 g, yield: 96%).

Provenance & Evidence