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 1470952Notes

Reaction equation

HRID 1470952 reaction equation
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

Participants

9

Reactant 6

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

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 0.1 M 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%).

Workup

  1. concentrationSolution was concentrated and to the residue
  2. additionwas added 0.1 M 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

Sources & evidence

ORD record
ord-dac129ab9ffe4611b41633abe5efde7a
Source dataset
uspto-grants-2015_04
Patent number
US09006387B2

Reaction notes

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