1,1,1,3,3,3-Hexafluoro-2-propanol → (2S,3R,4R,5S)-2,5-bis(4-(benzyloxy)phenyl)-1-(4-tert-butylphenyl)pyrrolidine-3,4-diol

HRID 2364808ノート

反応式

HRID 2364808 の反応式
C[C:2]1([CH3:15])[O:6][C@H:5]([C@H:7](O)[CH2:8]O)[C@@H:4]([C@H:11](O)[CH2:12]O)O1.[C:16]([OH:19])(=O)[CH3:17].[C:20]([OH:23])(=O)[CH3:21].I[C:25]1[CH:30]=[CH:29]C=[CH:27][CH:26]=1.C([O-])(O)=O.[Na+].[C:36]([C:40]1[CH:46]=[CH:45][C:43]([NH2:44])=[CH:42][CH:41]=1)([CH3:39])([CH3:38])[CH3:37].[CH2:47]([O:54][C:55]1[CH:60]=[CH:59][C:58](B(O)O)=[CH:57][CH:56]=1)[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1.FC(F)(F)C(O)C(F)(F)F>CO.ClCCl>[CH2:47]([O:54][C:55]1[CH:60]=[CH:59][C:58]([C@H:17]2[C@@H:16]([OH:19])[C@H:20]([OH:23])[C@H:21]([C:12]3[CH:11]=[CH:4][C:5]([O:6][CH2:2][C:15]4[CH:29]=[CH:30][CH:25]=[CH:26][CH:27]=4)=[CH:7][CH:8]=3)[N:44]2[C:43]2[CH:42]=[CH:41][C:40]([C:36]([CH3:39])([CH3:37])[CH3:38])=[CH:46][CH:45]=2)=[CH:57][CH:56]=1)[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1

参加物

9

反応物 6

HCID 135291,1,1,3,3,3-Hexafluoro-2-propanolHCID 698614-Tert-ButylanilineHCID 516892Sodium BicarbonateHCID 27343144-Benzyloxy-phenylboronic acidHCID 7096260HCID 7096260、化合物HCID 12217721Iodo benzene diacetate

生成物 1

HCID 67238023(2S,3R,4R,5S)-2,5-bis(4-(benzyloxy)phenyl)-1-(4-tert-butylphenyl)pyrrolidine-3,4-diol収率 46.1%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒

実験手順

To a solution of (1R,1′R)-1,1′-((4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-diyl)diethane-1,2-diol (200 mg, 0.90 mmol) in methanol (6 ml) and dichloromethane (3 ml) was added iodobenzene diacetate (696 mg, 2.16 mmol) and the solution was stirred at room temperature for 5 h. Solution was concentrated and to the residue was added 0.1M H2SO4 (4 ml) and stirring was continued at room temperature for 18 h. The pH was adjusted to ˜6 with solid NaHCO3, and 4-tert-butylaniline (287 μl, 1.80 mmol) was added followed by 4-benzyloxyphenylboronic acid (369 mg, 1.62 mmol) and hexafluoroisopropyl alcohol (4 ml) and stirred at 60° C. for 2 h. Solvent was concentrated and the residue dissolved in ethyl acetate, washed with H2O, 0.33M K3PO4, brine, dried (Na2SO4), filtered and concentrated to give crude product which was purified by chromatography on silica gel eluting with 0-20% ethyl acetate/dichloromethane to give title compound (249 mg, 46%).

後処理

  1. concentrationSolution was concentrated and to the residue
  2. additionwas added 0.1M H2SO4 (4 ml)
  3. stirringstirring
  4. waitwas continued at room temperature for 18 h
  5. additionwas added
  6. stirringstirred at 60° C. for 2 h
  7. concentrationSolvent was concentrated
  8. dissolutionthe residue dissolved in ethyl acetate
  9. washwashed with H2O, 0.33M K3PO4, brine
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto give crude product which
  14. customwas purified by chromatography on silica gel eluting with 0-20% ethyl acetate/dichloromethane

出典と根拠

ORDレコード
ord-f8188921500b416c8b9176de368480ff
出典データセット
uspto-grants-2014_04
特許番号
US08691938B2

反応ノート

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