Sodium hydride → (S)-(-)-4,4,4-Trifluoro-3-hydroxy-3-methyl-1-(4-phenylsulfonylphenyl)-trans-but-1-ene

HRID 35892Notes

Reaction equation

HRID 35892 reaction equation
[F:1][C:2]([F:25])([F:24])[C@@:3]([CH3:23])([OH:22])[CH:4](O)[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)(=[O:14])=[O:13])=[CH:8][CH:7]=1.[H-].[Na+]>O1CCCC1>[F:25][C:2]([F:1])([F:24])[C@:3]([OH:22])([CH3:23])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[CH:8][C:9]([S:12]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)(=[O:14])=[O:13])=[CH:10][CH:11]=1

Participants

4

Reactant 2

HCID 24758Sodium hydride3×HCID 57137960(2S)-1,1,1-Trifluoro-2-methyl-4-(4-phenylsulfonylphenyl)-2,3-butanediol

Product 1

HCID 67708369(S)-(-)-4,4,4-Trifluoro-3-hydroxy-3-methyl-1-(4-phenylsulfonylphenyl)-trans-but-1-eneYield 68.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a tetrahydrofuran (5 mL) solution of (2S)-1,1,1-trifluoro-2-methyl-4-(4-phenylsulfonylphenyl)-2,3-butanediol (product described in Example 13.d.) (500 mg, 1.34 mmol) was added sodium hydride (60 mg, 60% at dispersion, 1.57 mmol). The mixture was heated to 65° C. After 10 minutes, another aliquot of sodium hydride (60 mg, 60% oil dispersion, 1.57 mmol) was added. The mixture was heated to reflux (66° C. internal temp.) for 1.5 hours, after which time a third aliquot of sodium hydride (40 mg, 60% oil dispersion, 1.04 mmol) was added. The reaction was heated to reflux for 2.0 additional hours, then cooled to ambient temperature and stirred for an additional 1.6 hours. The reaction was quenched with water and the product extracted into diethyl ether. The organic extracts were dried and evaporated. The crude product was purified by chromatography, with diethyl ether:dichloromethane as the eluent (gradient, 0:100 to 2:98) to give the title compound as a white solid (326 mg, 68%). See Example 13 for characterization data.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux (66° C. internal temp.) for 1.5 hours
  3. temperatureThe reaction was heated
  4. temperatureto reflux for 2.0 additional hours
  5. temperaturecooled to ambient temperature
  6. customThe reaction was quenched with water
  7. extractionthe product extracted into diethyl ether
  8. customThe organic extracts were dried
  9. customevaporated
  10. customThe crude product was purified by chromatography, with diethyl ether

Sources & evidence

ORD record
ord-11bcd5e853b644cdab23b58928faf0bd
Source dataset
uspto-grants-1995_05
Patent number
US05411973

Reaction notes

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