Sodium Sulfite → 2,3-Difluoro-6-methoxyphenol

To a solution of 2,3-difluoro-6-methoxybenzaldehyde (2.58 g) in methylene chloride (45 mL) was added 3-chloroperbenzoic acid (5.97 g) under ice-cooling, and the mixture was heated for reflux overnight. The reaction mixture was cooled in ice. To the mixture was added 10% aqueous sodium sulfite solution, and the resulting mixture was stirred for 20 minutes. The organic layer was separated and washed with water twice, a saturated aqueous sodium hydrogen carbonate solution, water and brine successively, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was dissolved in tetrahydrofuran (15 mL)-methanol (7.5 mL). To the solution was added sodium methoxide (28% methanol solution, 3.75 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into 1 mol/L hydrochloric acid, and the resulting mixture was extracted with ethyl acetate. The extract was washed with brine and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane−n-hexane/ethyl acetate=2/3) and column chromatography on aminopropylated silica gel (eluent: ethyl acetate/methanol=9/1−3/2) successively to give the title compound (1.7 g).

1. temperaturecooling
2. temperaturethe mixture was heated
3. temperaturefor reflux overnight
4. temperatureThe reaction mixture was cooled in ice
5. customThe organic layer was separated
6. washwashed with water twice
7. dry with materiala saturated aqueous sodium hydrogen carbonate solution, water and brine successively, and dried over anhydrous magnesium sulfate
8. customThe solvent was removed under reduced pressure
9. dissolutionthe residue was dissolved in tetrahydrofuran (15 mL)-methanol (7.5 mL)
10. additionTo the solution was added sodium methoxide (28% methanol solution, 3.75 mL)
11. stirringthe mixture was stirred at room temperature for 1 hour
12. additionThe reaction mixture was poured into 1 mol/L hydrochloric acid
13. extractionthe resulting mixture was extracted with ethyl acetate
14. washThe extract was washed with brine
15. dry with materialdried over anhydrous magnesium sulfate
16. customThe solvent was removed under reduced pressure
17. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane−n-hexane/ethyl acetate=2/3) and column chromatography on aminopropylated silica gel (eluent: ethyl acetate/methanol=9/1−3/2) successively

ORD 기록

ord-58326b823453412f8fe29a84a6459a3a

출처 데이터셋

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09040693B2