Methanol → HCID 72261985, compound

HRID 1466434Notes

Reaction equation

HRID 1466434 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]([C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([S:28]([CH3:31])(=[O:30])=[O:29])[CH:23]=3)=[CH:18][CH:17]=2)[CH:10]=[C:11]([C:13](=O)[CH3:14])[N:12]=1.Cl.[NH2:33][OH:34].C([O-])(=O)C.[Na+].CO>CCOC(C)=O.O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]([C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([S:28]([CH3:31])(=[O:30])=[O:29])[CH:23]=3)=[CH:18][CH:17]=2)[CH:10]=[C:11]([C:13](=[N:33][OH:34])[CH3:14])[N:12]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 443297Hydroxyamine hydrochlorideHCID 517045Sodium AcetateHCID 59251503HCID 59251503, compound

Product 1

HCID 72261985HCID 72261985, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a 50 mL RB flask attached with Vigreux column was added compound 1-[2-(2-Chloro-phenyl)-1-(3′-methanesulfonyl-biphenyl-4-yl)-1H-imidazol-4-yl]-ethanone (162 mg, 359 μmol), hydroxylamine-HCl (200 mg, 2.87 mmol), sodium acetate (238 mg, 2.90 mmol), MeOH (12 mL) and H2O (6 mL). The reaction solution was allowed to stir at reflux for 2 hrs prior to TLC analysis. The reaction solution was diluted with EtOAc (150 mL), washed with aq. NaCl (100 mL), partitioned, dried over Na2SO4, filtered, and concentrated on the Rotavapor. The crude product was chromatographed through a 25 g SiO2 column using a mobile phase gradient of 100% Hx to 80% EtOAc to afford 85 mg (51% yield) of the title compound as a mixture of E and Z isomers. The isomers were separated by chromatography with a Reverse Phase HPLC using a C18 Preparative column. Characterization for one single oxime isomer: 1H NMR (400 MHz, DMSO-d6) δ 9.86 (s, 1H), 8.15 (t, 1H), 8.02 (d, 1H), 7.90 (d, 1H), 7.85 (s, 1H), 7.80 (d, 2H), 7.72 (t, 1H), 7.64 (d, 1H), 7.47-7.44 (m, 3H), 7.35 (d, 2H); MS (ES): 466.1 [M+H]+.

Workup

  1. temperatureat reflux for 2 hrs
  2. washwashed with aq. NaCl (100 mL)
  3. custompartitioned
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated on the Rotavapor
  7. customThe crude product was chromatographed through a 25 g SiO2 column

Sources & evidence

ORD record
ord-e21879be47604c84bb6c91cfd924aaa9
Source dataset
uspto-grants-2015_04
Patent number
US09000022B2

Reaction notes

Loading…