Water → rac-(3S*,5S*)-5-(2,6-dimethoxyphenyl)-3-methoxy-1-(4-(trifluoromethoxy)benzyl)pyrrolidin-2-one

HRID 594400ノート

反応式

HRID 594400 の反応式
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[CH:11]1[N:15]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=2)[C:14](=[O:28])[CH:13]([OH:29])[CH2:12]1.[H-].[Na+].[CH3:32]I.O>C1COCC1.CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[CH:11]1[N:15]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]([F:25])([F:26])[F:27])=[CH:19][CH:18]=2)[C:14](=[O:28])[CH:13]([O:29][CH3:32])[CH2:12]1

参加物

7

反応物 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 69082591rac-(3S*,5S*)-5-(2,6-dimethoxyphenyl)-3-hydroxy-1-(4-(trifluoromethoxy)benzyl)pyrrolidin-2-one

生成物 1

HCID 69081617rac-(3S*,5S*)-5-(2,6-dimethoxyphenyl)-3-methoxy-1-(4-(trifluoromethoxy)benzyl)pyrrolidin-2-one

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

A cooled (0° C.) solution of rac-(3S*,5S*)-5-(2,6-dimethoxyphenyl)-3-hydroxy-1-(4-(trifluoromethoxy)benzyl)pyrrolidin-2-one (53 mg; 0.12 mmol) in anh. THF (3 ml) was treated with NaH (60% dispersion in mineral oil; 6 mg; 0.14 mmol). Stirring was continued at 0° C., under nitrogen, for 5 min., and then at rt for 20 min. The mixture was again cooled to 0° C., and a solution of CH3I (20 mg; 0.14 mmol) in anh. THF (1 ml) was added. The obtained mixture was further stirred at 0° C. for 5 min., and then at rt for 17 h. Water and AcOEt were added, and the separated aq. layer was further extracted with AcOEt. The mixed organic layers were dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH=30/1) afforded rac-(3S*,5S*)-5-(2,6-dimethoxyphenyl)-3-methoxy-1-(4-(trifluoromethoxy)benzyl)pyrrolidin-2-one as a yellow oil. LC-MS (conditions A): tR=0.88 min.; [M+H]+: 426.19 g/mol.

後処理

  1. waitat rt for 20 min
  2. stirringThe obtained mixture was further stirred at 0° C. for 5 min.
  3. waitat rt for 17 h
  4. extractionthe separated aq. layer was further extracted with AcOEt
  5. dry with materialThe mixed organic layers were dried over anh. MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure
  8. customPurification by FC (DCM/MeOH=30/1)

出典と根拠

ORDレコード
ord-1163e61755874947b0c535befc10ba80
出典データセット
uspto-grants-2016_01
特許番号
US09242970B2

反応ノート

読み込み中…