Toluene → HCID 178475413, compound

HRID 1059259Notes

Reaction equation

HRID 1059259 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([OH:24])=[CH:10][CH:11]=[C:12]([C:14]([OH:23])([C:18]3[N:19]=[CH:20][NH:21][CH:22]=3)[CH:15]([CH3:17])[CH3:16])[CH:13]=2)=[CH:4][CH:3]=1.[C:25](OC(=O)C)(=[O:27])[CH3:26].C1(C)C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>N1C=CC=CC=1.C(OCC)(=O)C.CO>[C:25]([O:24][C:9]1[CH:10]=[CH:11][C:12]([C:14]([OH:23])([C:18]2[N:19]=[CH:20][NH:21][CH:22]=2)[CH:15]([CH3:17])[CH3:16])=[CH:13][C:8]=1[C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)(=[O:27])[CH3:26]

Participants

8

Reactant 4

HCID 1140TolueneHCID 6101p-Toluenesulfonic acidHCID 7918Acetic Anhydride2×HCID 178450197HCID 178450197, compound

Product 1

HCID 178475413HCID 178475413, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4′-fluoro-5-[1-hydroxy-1-(1H-imidazol-4-yl)-2-methylpropyl][1,1′-biphenyl]-2-ol (390 mg) in pyridine (4 ml) was added dropwise acetic anhydride (0.135 ml) at room temperature, and the mixture was stirred for 4 h. Acetic anhydride (22.5 μl) was further added and the mixture was stirred for 15 h. The reaction mixture was subjected to azeotropic reaction with toluene for concentration, diluted with ethyl acetate, washed with water and saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and to a solution of the residue (414 mg) in pyridine (4 ml) was added dropwise acetic anhydride (0.209 ml) at room temperature. The mixture was stirred for 15 h and the reaction mixture was subjected to azeotropic reaction with toluene for concentration. To a solution of the residue in methanol (15 ml) was added 0.1N aqueous p-toluenesulfonic acid solution (7.5 ml) at room temperature, and the mixture was stirred for 1 h. The reaction mixture was concentrated, diluted with ethyl acetate, neutralized with saturated aqueous sodium hydrogen carbonate, extracted with ethyl acetate, washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by column chomatography (eluent; ethyl acetate→ethyl acetate:methanol=20:1) to give the colorless amorphous title compound (337 mg).

Workup

  1. stirringthe mixture was stirred for 15 h
  2. washwashed with water and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure and to a solution of the residue (414 mg) in pyridine (4 ml)
  5. additionwas added dropwise acetic anhydride (0.209 ml) at room temperature
  6. stirringThe mixture was stirred for 15 h
  7. customthe reaction mixture was subjected to azeotropic reaction with toluene for concentration
  8. stirringthe mixture was stirred for 1 h
  9. concentrationThe reaction mixture was concentrated
  10. additiondiluted with ethyl acetate
  11. extractionextracted with ethyl acetate
  12. washwashed with saturated brine
  13. dry with materialdried over anhydrous magnesium sulfate
  14. customThe solvent was evaporated under reduced pressure
  15. customthe residue was purified by column chomatography (eluent; ethyl acetate→ethyl acetate:methanol=20:1)

Sources & evidence

ORD record
ord-d12dd8560b2d4a02baab9f844cc84562
Source dataset
uspto-grants-2003_02
Patent number
US06518257B1

Reaction notes

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