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

Temperature

-20 °C

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%).

1. customwas synthesized
2. stirringit was further stirred at room temperature for 40 minutes
3. temperatureAfter the reaction mixture was cooled to −30° C.
4. stirringthe mixture was further stirred at room temperature for 1 hour
5. additionAfter the reaction mixture was carefully poured
6. extractionthe mixture was extracted with ethyl acetate (three times)
7. washthe organic layer was successively washed with 1N hydrochloric acid
8. dry with materiala 5% aqueous sodium hydrogencarbonate solution, water (twice) and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate
9. customThe residue obtained
10. customby removing the solvent under reduced pressure
11. customwas purified by silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=20/1-10/1)
12. waitThe obtained 2-(tetrahydro-2H-pyran-2-yloxy)-3-(trifluoromethyl)benzaldehyde as a pale yellow oil was left
13. waitto stand at room temperature overnight

ORD record

ord-e718ce97c4bf4225aaccc06ebc6dee96

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07923573B2