Boron trifluoride etherate → 2-(4-Fluorophenyl)-1-[4-(phenylsulfonyl)phenyl]ethanol

Temperature

-40 °C

Lithium chloride (0.57 g, 13.5 mmol, dried at 140° C. under vacuum) and copper(I) cyanide (0.605 g, 6.8 mmol) were dissolved in tetrahydrofuran (5 mL) and cooled to −40° C. under nitrogen. 4-Fluorobenzylzinc chloride (0.5M in tetrahydrofuran, 15 mL) was added dropwise and the solution cooled to −20° C. for 5 minutes then to −78° C. Boron trifluoride diethyl etherate (1.7 mL, 13.5 mmol) and 4-(phenylsulfonyl)benzaldehyde (Example 113 Step 1, 300 mg, 1.2 mmol) in tetrahydrofuran (5 mL) were added and the reaction stirred at −78° C. for 30 minutes then warmed to 25° C. and quenched with saturated ammonium chloride solution. Ethyl acetate was added and the mixture stirred for 10 minutes then the layers separated. The organic layer was washed with brine, dried over MgSO4 and evaporated. The residue was purified by flash column chromatography on silica, eluting with 40% ethyl acetate/isohexane, to give the title compound as a white solid (0.386 g, 90%). δH (360 MHz, CDCl3): 7.94-7.88 (4H, m), 7.58-7.43 (5H, m), 7.10-7.02 (2H, m), 6.99-6.93 (2H, m), 4.92-4.88 (1H, m), 2.99-2.85 (2H, m), 2.01 (1H, d, J=3.2 Hz).

1. temperaturethe solution cooled to −20° C. for 5 minutes
2. customto −78° C
3. temperaturethen warmed to 25° C.
4. customquenched with saturated ammonium chloride solution
5. additionEthyl acetate was added
6. stirringthe mixture stirred for 10 minutes
7. customthe layers separated
8. washThe organic layer was washed with brine
9. dry with materialdried over MgSO4
10. customevaporated
11. customThe residue was purified by flash column chromatography on silica
12. washeluting with 40% ethyl acetate/isohexane

ORD record

ord-e1d72f8eae004361869de80c87eca933

Source dataset

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07468393B2