Tetrahydrofuran → (S)-4-(5-chloro-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-ol

HRID 854168

Reaktionsgleichung

Reaktionsgleichung von HRID 854168
[CH3:1][S@:2]([C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][CH:5]=1)=[O:3].C1CCCCC1.[Cl:17][C:18]1[CH:19]=[C:20]([C:27]([CH3:36])([CH3:35])[CH2:28][C:29](=[O:34])[C:30]([F:33])([F:32])[F:31])[C:21]2[O:25][CH2:24][CH2:23][C:22]=2[CH:26]=1.C1COCC1>>[Cl:17][C:18]1[CH:19]=[C:20]([C:27]([CH3:36])([CH3:35])[CH2:28][C@:29]([CH2:1][S@:2]([C:4]2[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][CH:5]=2)=[O:3])([OH:34])[C:30]([F:31])([F:32])[F:33])[C:21]2[O:25][CH2:24][CH2:23][C:22]=2[CH:26]=1.[Cl:17][C:18]1[CH:19]=[C:20]([C:27]([CH3:36])([CH3:35])[CH2:28][C@@:29]([CH2:1][S@:2]([C:4]2[CH:9]=[CH:8][C:7]([CH3:10])=[CH:6][CH:5]=2)=[O:3])([OH:34])[C:30]([F:31])([F:32])[F:33])[C:21]2[O:25][CH2:24][CH2:23][C:22]=2[CH:26]=1

Komponenten

6

Edukt 4

HCID 8028Tetrahydrofuran2×HCID 8078CyclohexaneHCID 10913262(R)-Methyl p-tolylsulfoxideHCID 469392144-(5-Chloro-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methylpentan-2-one

Produkt 2

HCID 69416142(S)-4-(5-chloro-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-olAusbeute 55 %HCID 69418747(R)-4-(5-chloro-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-olAusbeute 25 %

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. 4-(5-Chloro-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methylpentan-2-one (1.81 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)-4-(5-chloro-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-ol (1.49 g, 55%) and (R)-4-(5-chloro-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-((R)-toluene-4-sulfinylmethyl)pentan-2-ol (670 mg, 25%). 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-f51dddc9e8a342f4a99d1388fc02104e
Quelldatensatz
uspto-grants-2007_08
Patentnummer
US07256300B2

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