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

HRID 1047486Notes

Reaction equation

HRID 1047486 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH2:11][C:12]2[C:17]([F:18])=[C:16]([F:19])[CH:15]=[CH:14][C:13]=2[F:20])(=[O:10])=[O:9])=[CH:4][CH:3]=1.C([Li])CCC.[CH2:26]1[O:29][CH:27]1[CH3:28]>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([CH:11]([C:12]2[C:13]([F:20])=[CH:14][CH:15]=[C:16]([F:19])[C:17]=2[F:18])[CH2:26][CH:27]([OH:29])[CH3:28])(=[O:10])=[O:9])=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6378Propylene OxideHCID 589503342-(4-Chloro-benzenesulfonylmethyl)-1,3,4-trifluoro-benzeneHCID 178418339Butyllithium

Product 1

HCID 589505814-(4-Chloro-benzenesulfonyl)-4-(2,3,6-trifluoro-phenyl)-butan-2-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-67219acf333c448a82a253d715f1cbab
Source dataset
uspto-grants-2013_10
Patent number
US08569521B2

Reaction notes

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