Cyclobutanone → 1-(2,3-Difluoro-6-methoxyphenyl)-1-cyclobutanol

To a solution of 3,4-difluoroanisole (2.47 g) in tetrahydrofuran (50 mL) was added n-butyllithium (2.64 mol/L n-hexane solution, 6.5 mL) at −78° C., and the mixture was stirred at the same temperature for 30 minutes. To the reaction mixture was added a solution of cyclobutanone (1 g) in tetrahydrofuran (20 mL), and the mixture was stirred at the same temperature for 30 minutes. To the reaction mixture was added a saturated aqueous ammonium chloride solution, and the resulting mixture was extracted with diethyl ether. The extract was washed with water and brine successively, 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/ethyl acetate=5/1) to give the title compound (2.69 g).

1. stirringthe mixture was stirred at the same temperature for 30 minutes
2. extractionthe resulting mixture was extracted with diethyl ether
3. washThe extract was washed with water and brine successively
4. dry with materialdried over anhydrous magnesium sulfate
5. customThe solvent was removed under reduced pressure
6. customthe residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=5/1)

ORD record

ord-45f06d753e55429f876bd61caeebbfe9

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09040693B2