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

HRID 2387300Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2387300
[CH3:1][S@:2]([C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][CH:5]=1)=[O:3].O1CCCC1.C([N-]C(C)C)(C)C.[Li+].[F:24][C:25]([F:41])([F:40])[C:26](=[O:39])[CH2:27][C:28]([C:31]1[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=1[CH3:38])([CH3:30])[CH3:29]>C1COCC1.C1CCCCC1>[F:41][C:25]([F:24])([F:40])[C@@:26]([CH2:1][S@:2]([C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][CH:5]=1)=[O:3])([OH:39])[CH2:27][C:28]([C:31]1[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=1[CH3:38])([CH3:30])[CH3:29]

Komponenten

6

Edukt 3

HCID 10913262(R)-Methyl p-tolylsulfoxideHCID 10997623Lithium diisopropylamide mono(tetrahydrofuran)HCID 207961201,1,1-Trifluoro-4-(5-fluoro-2-methylphenyl)-4-methylpentan-2-one

Produkt 1

HCID 58933190(S)-1,1,1-trifluoro-4-(5-fluoro-2-methylphenyl)-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-olAusbeute 55,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8028TetrahydrofuranLösungsmittel2×HCID 8078CyclohexaneLösungsmittel

Versuchsvorschrift

To a suspension of (R)-(+)-methyl p-tolylsulfoxide (23.6 g, 153 mmol) in 200 mL of anhydrous THF at −78° C. was added lithium diisopropylamide mono(tetrahydrofuran) (LDA), 1.5 M solution in cyclohexane, 102 mL, 153 mmol) over 20 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 (36.4 g, 139 mmol) was then added via cannula with the aid of 125 mL of THF over 30 minutes. After 1.5 hours at −78° C., the reaction mixture was quenched with 600 mL of water and extracted with two 500 mL portions of ethyl acetate. The combined organic phases were washed with saturated aqueous sodium bicarbonate solution and brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. Purification by column chromatography with silica gel (eluted with 10%-30% EtOAc/hexanes) afforded sequentially (S)-1,1,1-trifluoro-4-(5-fluoro-2-methylphenyl)-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-ol (31.9 g, 55%, 99% de) and (R)-1,1,1-trifluoro-4-(5-fluoro-2-methylphenyl)-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-ol.

Aufarbeitung

  1. waitAfter 1.5 hours at −78° C.
  2. customthe reaction mixture was quenched with 600 mL of water
  3. extractionextracted with two 500 mL portions of ethyl acetate
  4. washThe combined organic phases were washed with saturated aqueous sodium bicarbonate solution and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification by column chromatography with silica gel (eluted with 10%-30% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-9f57eaaf2f1848d88514b79f1f48ffdc
Quelldatensatz
uspto-grants-2012_09
Patentnummer
US08268859B2

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