Tetrahydrofuran → (S)-1,1,1-trifluoro-4-(5-fluoro-2-methylphenyl)-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-ol

HRID 854165Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 854165
[CH3:1][S@:2]([C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][CH:5]=1)=[O:3].C1CCCCC1.[F:17][C:18]([F:34])([F:33])[C:19](=[O:32])[CH2:20][C:21]([C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=1[CH3:31])([CH3:23])[CH3:22].C1COCC1>>[F:34][C:18]([F:17])([F:33])[C@@:19]([CH2:1][S@:2]([C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][CH:5]=1)=[O:3])([OH:32])[CH2:20][C:21]([C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=1[CH3:31])([CH3:23])[CH3:22].[F:34][C:18]([F:17])([F:33])[C@:19]([CH2:1][S@:2]([C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][CH:5]=1)=[O:3])([OH:32])[CH2:20][C:21]([C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=1[CH3:31])([CH3:23])[CH3:22]

Komponenten

6

Edukt 4

HCID 8028Tetrahydrofuran2×HCID 8078CyclohexaneHCID 10913262(R)-Methyl p-tolylsulfoxideHCID 207961201,1,1-Trifluoro-4-(5-fluoro-2-methylphenyl)-4-methylpentan-2-one

Produkt 2

HCID 58933190(S)-1,1,1-trifluoro-4-(5-fluoro-2-methylphenyl)-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-olAusbeute 58 %HCID 67132212(R)-1,1,1-trifluoro-4-(5-fluoro-2-methylphenyl)-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-olAusbeute 27 %

Versuchsvorschrift

To a suspension of (R)-(+)-methyl p-tolylsulfoxide (1.00 g, 6.48 mmol) in 10 mL of anhydrous THF at −78° C. was added LDA mono(tetrahydrofuran), 1.5 M solution in cyclohexane (4.32 mL, 6.48 mmol) over 5 minutes. The resulting clear yellow solution was stirred for an additional 15 minutes. 1,1,1-Trifluoro-4-(5-fluoro-2-methylphenyl)-4-methylpentan-2-one (1.55 g, 5.90 mmol) was then added via cannula with the aid of 4 mL of THF over 5 minutes. After 1 hour at −78° C., the reaction mixture was quenched with 50 mL of water and extracted with three 50 mL portions of EtOAc. The combined organic phases were washed with saturated aqueous sodium bicarbonate solution, brine, dried over sodium sulfate, filtered, and concentrated in vacuo. Purification by column chromatography with silica gel (eluted with 15%-25% EtOAc/hexanes) afforded sequentially (S)-1,1,1-trifluoro-4-(5-fluoro-2-methylphenyl)-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-ol (1.42 g, 58%) and (R)-1,1,1-trifluoro-4-(5-fluoro-2-methylphenyl)-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-ol (665 mg, 27%). The diastereomeric excess was determined to be >99% for both isomers (HPLC peak area).

Aufarbeitung

  1. waitAfter 1 hour at −78° C.
  2. customthe reaction mixture was quenched with 50 mL of water
  3. extractionextracted with three 50 mL portions of EtOAc
  4. washThe combined organic phases were washed with saturated aqueous sodium bicarbonate solution, brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by column chromatography with silica gel (eluted with 15%-25% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-cdf3f67356d54973b24db57cae7bec68
Quelldatensatz
uspto-grants-2007_08
Patentnummer
US07256300B2

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