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

HRID 854162Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 854162
[CH3:1][S@:2]([C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][CH:5]=1)=[O:3].C([N-]C(C)C)(C)C.[Li+].C1CCCCC1.[F:25][C:26]([F:43])([F:42])[C:27](=[O:41])[CH2:28][C:29]([C:32]1[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=1[O:39][CH3:40])([CH3:31])[CH3:30]>C1COCC1>[F:43][C:26]([F:25])([F:42])[C@@:27]([CH2:1][S@:2]([C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][CH:5]=1)=[O:3])([OH:41])[CH2:28][C:29]([C:32]1[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=1[O:39][CH3:40])([CH3:31])[CH3:30].[F:43][C:26]([F:25])([F:42])[C@:27]([CH2:1][S@:2]([C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][CH:5]=1)=[O:3])([OH:41])[CH2:28][C:29]([C:32]1[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:33]=1[O:39][CH3:40])([CH3:31])[CH3:30]

Komponenten

7

Edukt 4

HCID 8078CyclohexaneHCID 2724682Lithium diisopropylamideHCID 100849201,1,1-Trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methylpentan-2-oneHCID 10913262(R)-Methyl p-tolylsulfoxide

Produkt 2

HCID 16115562(S)-1,1,1-trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-olAusbeute 62 %HCID 16115563(R)-1,1,1-trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-olAusbeute 29 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a suspension of (R)-(+)-methyl p-tolylsulfoxide (28.2 g, 183 mmol) in 200 mL of anhydrous THF at −78° C. was added lithium diisopropylamide (LDA) mono(tetrahydrofuran), 1.5 M solution in cyclohexane (122 mL, 183 mmol) over 30 minutes. The resulting clear yellow solution was stirred for an additional 15 minutes. 1,1,1-Trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methylpentan-2-one (46.3 g, 166 mmol) dissolved in 125 mL of THF was then added via cannula over 30 minutes. After 1.5 hours at −78° C., the reaction mixture was quenched with 600 mL of water and extracted first with a 600 mL portion of EtOAc and then a 400 mL portion of EtOAc. The combined organic phases were washed with saturated aqueous sodium bicarbonate (NaHCO3) solution, washed with brine, dried over sodium sulfate (Na2SO4), 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-methoxyphenyl)-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-ol (44.2 g, 62%) and (R)-1,1,1-trifluoro-4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-ol (20.6 g, 29%). The diastereomeric excess was determined to be >99% for both isomers (HPLC peak area).

Aufarbeitung

  1. additionwas then added via cannula over 30 minutes
  2. waitAfter 1.5 hours at −78° C.
  3. customthe reaction mixture was quenched with 600 mL of water
  4. extractionextracted first with a 600 mL portion of EtOAc
  5. washThe combined organic phases were washed with saturated aqueous sodium bicarbonate (NaHCO3) solution
  6. washwashed with brine
  7. dry with materialdried over sodium sulfate (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification by column chromatography with silica gel (eluted with 10%-30% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-195bf8320b3c4deca636e4f408bcb0fb
Quelldatensatz
uspto-grants-2007_08
Patentnummer
US07256300B2

Notizen zur Reaktion

Wird geladen…