Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1) → (2R)-1-(2,4-difluorophenyl)-2-hydroxypropan-1-one

Temperature

55 °C

(2R)-2′,4′-Difluoro-2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propiophenone (9.62 g, 35.6 mmol, synthesized according to the description in Chem. Pharm. Bull., Vol. 41(6), 1035-1042 (1993)) was dissolved in ethanol (99.5%, 50 mL), and pyridinium p-toluenesulfonate (0.89 g, 3.6 mmol) was added. The mixture was stirred at 50-60° C. for 1 hr. After cooling, the reaction mixture was concentrated under reduced pressure to about 10 mL. Water (20 mL) was flown in and the mixture was extracted twice with ethyl acetate (50 mL). The layers extracted with ethyl acetate were mixed, washed with saturated brine (20 mL) and dried over anhydrous magnesium sulfate. After filtration, the filtrate (ethyl acetate solution) was concentrated. The obtained concentrate (about 9.5 g) was subjected to silica gel column chromatography (SiO2, 30 g) and eluted with n-heptane-ethyl acetate (10:1→5:1). The objective fraction was concentrated to give the title compound as a pale-yellow oil (6.00 g, yield: 91%).

1. temperatureAfter cooling
2. concentrationthe reaction mixture was concentrated under reduced pressure to about 10 mL
3. extractionwas extracted twice with ethyl acetate (50 mL)
4. extractionThe layers extracted with ethyl acetate
5. additionwere mixed
6. washwashed with saturated brine (20 mL)
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationAfter filtration
9. concentrationthe filtrate (ethyl acetate solution) was concentrated
10. concentrationThe obtained concentrate (about 9.5 g)
11. washeluted with n-heptane-ethyl acetate (10:1→5:1)
12. concentrationThe objective fraction was concentrated

ORD record

ord-af355d4ca78b422286ca1133420ed6af

Source dataset

uspto-grants-2007_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07297802B2