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ノート

反応式

HRID 854168 の反応式
[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

参加物

6

反応物 4

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

生成物 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-ol収率 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-ol収率 25%

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-f51dddc9e8a342f4a99d1388fc02104e
出典データセット
uspto-grants-2007_08
特許番号
US07256300B2

反応ノート

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