Benzcatechinborane → 2,2-difluoro-1(R)-(4-fluorophenyl)-2-(4-methylsulfanylphenoxy)ethanol

Temperature

-70 °C

To a solution of 2,2-difluoro-1-(4-fluorophenyl)-2-(4-methylsulfanylphenoxy)ethanone (2.76 g, 8.84 mmol) and S-methyl-CS-oxazaborolidine in a mixture of DCM/Toluene (1/1, 40 ml) under nitrogen, at −70° C., a solution of catecholborane (1.27 g, 10.6 mmol) in DCM (2 ml) was slowly added. After stirring at −70° C. for 18 h, the reaction mixture was quenched by adding 4M solution of HCl in dioxane (3 ml). The heterogeneous mixture was stirred for 15 min at −70° C., then warmed to room temperature. Solvent was removed on a rotary evaporator and the resulting solution was diluted with hexanes (80 ml). Water (0.5 ml) was added and the mixture was stirred for 15 min. The solids were filtered and the filter cake was washed with hexanes. The filtrate was washed with 10% aqueous sodium metabisulfite (15 ml) and brine (15 ml). The organic phase was dried over sodium sulfate and the crude purified by flash chromatography, using EA/H (1/10) as eluent to give 2,2-difluoro-1(R)-(4-fluorophenyl)-2-(4-methylsulfanylphenoxy)ethanol (1.55 g, 56%) as a white solid.

1. customthe reaction mixture was quenched
2. additionby adding 4M solution of HCl in dioxane (3 ml)
3. stirringThe heterogeneous mixture was stirred for 15 min at −70° C.
4. temperaturewarmed to room temperature
5. customSolvent was removed on a rotary evaporator
6. additionthe resulting solution was diluted with hexanes (80 ml)
7. additionWater (0.5 ml) was added
8. stirringthe mixture was stirred for 15 min
9. filtrationThe solids were filtered
10. washthe filter cake was washed with hexanes
11. washThe filtrate was washed with 10% aqueous sodium metabisulfite (15 ml) and brine (15 ml)
12. dry with materialThe organic phase was dried over sodium sulfate
13. customthe crude purified by flash chromatography

ORD record

ord-b4410dd13b024685bb29e56ef06593f4

Source dataset

uspto-grants-2011_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08013186B2