Propylene Oxide → 4-(4-Chloro-benzenesulfonyl)-4-(2,3,6-trifluoro-phenyl)-butan-2-ol

Temperatur

-78 °C

2-(4-Chloro-benzenesulfonylmethyl)-1,3,4-trifluoro-benzene (Example 8, step 2, 305 mg, 0.95 mmol) was dissolved in 4 mL THF. The solution was cooled to −78° C. and butyllithium (2.5M in hexane, 0.4 mL) was added slowly. The solution was stirred at −78° C. for 2 h then warmed to 0° C. and stirred for 0.5 h. The solution was then cooled to −78° C. again and propylene oxide (178.0 mg, 3.1 mmol) in 3.25 mL of THF was added slowly and the reaction mixture was allowed to stir and warm to room temperature overnight. The reaction mixture was quenched with a saturated NH4Cl solution (50 mL). The reaction mixture was extracted three times with EtOAc (50 mL each) and the combined organics were washed with water (100 mL) and brine (100 mL). The organic layer was then dried over Na2SO4 and concentrated. The product was purified using column chromatography (hex./EtOAc 100/0 to 70/30 in 60 min. 0.19 g, 52%). 1H NMR (CDCl3 400 MHz) δ 7.59 (m, 2H), 7.42 (m, 2H), 7.10 (m, 1H), 6.81 (m, 0.5H), 6.66 (m, 0.5H), 4.83-4.99 (m, 1H), 4.06 (m, 0.5H), 3.51 (m, 0.5H), 2.50-2.74 (m, 1H), 2.26 (m, 1H), 1.03-2.24 (m, 3H). The product is a mixture of diastereomers.

1. temperaturethen warmed to 0° C.
2. stirringstirred for 0.5 h
3. temperatureThe solution was then cooled to −78° C. again
4. stirringto stir
5. temperaturewarm to room temperature overnight
6. customThe reaction mixture was quenched with a saturated NH4Cl solution (50 mL)
7. extractionThe reaction mixture was extracted three times with EtOAc (50 mL each)
8. washthe combined organics were washed with water (100 mL) and brine (100 mL)
9. dry with materialThe organic layer was then dried over Na2SO4
10. concentrationconcentrated
11. customThe product was purified
12. customcolumn chromatography (hex./EtOAc 100/0 to 70/30 in 60 min. 0.19 g, 52%)
13. additiona mixture of diastereomers

ORD-Eintrag

ord-e934f90ebb164477984ac5313a3da21e

Quelldatensatz

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08067621B2