Acetic Anhydride → HCID 18668579, compound

HRID 1059256Notes

Reaction equation

HRID 1059256 reaction equation
C1(C(=[N:14][C:15]2[C:20]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[CH:19][C:18]([C:28]([C:33]3[N:34]=[CH:35][N:36]([C:38]([C:51]4[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=4)([C:45]4[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=4)[C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)[CH:37]=3)([OH:32])[CH:29]([CH3:31])[CH3:30])=[CH:17][CH:16]=2)C2C=CC=CC=2)C=CC=CC=1.[C:57]([O-:60])(=O)[CH3:58].[Na+].[Cl-].O[NH3+].C(OC(=O)C)(=O)C.C(=O)([O-])O.[Na+]>C1COCC1.CO.C1COCC1.N1C=CC=CC=1>[F:27][C:24]1[CH:25]=[CH:26][C:21]([C:20]2[CH:19]=[C:18]([C:28]([OH:32])([C:33]3[N:34]=[CH:35][N:36]([C:38]([C:51]4[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=4)([C:45]4[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=4)[C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)[CH:37]=3)[CH:29]([CH3:31])[CH3:30])[CH:17]=[CH:16][C:15]=2[NH:14][C:57](=[O:60])[CH3:58])=[CH:22][CH:23]=1

Participants

9

Reactant 5

HCID 7918Acetic AnhydrideHCID 21645Hydroxylamine HClHCID 516892Sodium BicarbonateHCID 517045Sodium AcetateHCID 18668628HCID 18668628, compound

Product 1

HCID 18668579HCID 18668579, compoundYield 86.9%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a solution of 1-[6-[(diphenylmethylene)amino]-4′-fluoro[1,1′-biphenyl]-3-yl]-2-methyl-1-(1-trityl-1H-imidazol-4-yl)-1-propanol (110 mg) in THF-methanol (1:1) (6 ml) were added anhydrous sodium acetate (29.6 mg) and hydroxyammonium chloride (18.7 mg) at room temperature, and the mixture was stirred for 22 h. The reaction mixture was concentrated, diluted with ethyl acetate, washed with 0.5N aqueous sodium hydroxide solution and saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give a crude product (118 mg) of 1-[6-amino-4′-fluoro[1,1′-biphenyl]-3-yl]-2-methyl-1-(1-trityl-1H-imidazol-4-yl)-1-propanol as a yellow oil. To a solution of this product (116 mg) and pyridine (29.6 μl) in THF (2 ml) was added dropwise acetic anhydride (28.3 μl) at 0° C., and the mixture was stirred at room temperature for 16 h. Saturated aqueous sodium hydrogen carbonate was added to the reaction mixture and the mixture was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel chomatography (eluent; hexane:ethyl acetate=3:1→3:2) to give the colorless amorphous title compound (79.6 mg).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with ethyl acetate
  3. washwashed with 0.5N aqueous sodium hydroxide solution and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customto give a crude product (118 mg) of 1-[6-amino-4′-fluoro[1,1′-biphenyl]-3-yl]-2-methyl-1-(1-trityl-1H-imidazol-4-yl)-1-propanol as a yellow oil
  7. stirringthe mixture was stirred at room temperature for 16 h
  8. washthe mixture was washed with saturated brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customThe solvent was evaporated under reduced pressure
  11. customthe residue was purified by silica gel chomatography (eluent; hexane:ethyl acetate=3:1→3:2)

Sources & evidence

ORD record
ord-0213039948f24731abd8c1506a591326
Source dataset
uspto-grants-2003_02
Patent number
US06518257B1

Reaction notes

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