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 854168노트

반응식

HRID 854168 반응식
[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

참가 물질

6

반응물 4

HCID 8028Tetrahydrofuran2회HCID 8078CyclohexaneHCID 10913262(R)-Methyl p-tolylsulfoxideHCID 469392144-(5-Chloro-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methylpentan-2-one

생성물 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-ol수율 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-ol수율 25%

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-f51dddc9e8a342f4a99d1388fc02104e
출처 데이터셋
uspto-grants-2007_08
특허 번호
US07256300B2

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