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

HRID 854162ノート

反応式

HRID 854162 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].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]

参加物

7

反応物 4

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

生成物 2

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-195bf8320b3c4deca636e4f408bcb0fb
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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