Potassium Carbonate → HCID 60196594, compound

HRID 878270Notes

Reaction equation

HRID 878270 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:14]([CH3:28])[C:15](=[O:27])[C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([OH:26])[CH:17]=2)=[C:4]([O:29][CH3:30])[CH:3]=1.Br[CH2:32][CH2:33][O:34][CH3:35].CCN(C(C)C)C(C)C.C(=O)([O-])[O-].[K+].[K+].[NH4+].[Cl-]>C(#N)C.CCOC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:14]([CH3:28])[C:15](=[O:27])[C:16]2[CH:21]=[C:20]([C:22]([F:24])([F:23])[F:25])[CH:19]=[C:18]([O:26][CH2:32][CH2:33][O:34][CH3:35])[CH:17]=2)=[C:4]([O:29][CH3:30])[CH:3]=1

Participants

8

Reactant 5

HCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 809722-Bromoethyl methyl etherHCID 81531DiisopropylethylamineHCID 70663576HCID 70663576, compound

Product 1

HCID 60196594HCID 60196594, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of N-[4-(4-fluoro-2-methoxy-phenyl)-pyridin-3-yl]-3-hydroxy-N-methyl-5-trifluoromethyl-benzamide (0.06 g, 143 μmol) in acetonitrile (1 mL) were added 1-bromo-2-methoxyethane (19.8 mg, 143 μmol) and DIPEA (22.1 mg, 29.9 μL, 171 μmol) and the light yellow suspension was stirred at room temperature for 45 minutes. To the reaction mixture was added potassium carbonate (23.7 mg, 171 μmol) and stirring was continued for 2.75 hours at room temperature. Then the reaction mixture was stirred at reflux temperature for 16 hours. The reaction mixture was poured on saturated aqueous NH4Cl solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were dried over MgSO4, filtered, treated with silica gel and evaporated. The product was purified by preparative HPLC (Gemini NX column) using a gradient of MeOH:water (containing 0.1% formic acid) (20:80 to 98:2). Light brown solid (0.048 g; 70%). MS (ESI): m/z=479.16 [M+H]+.

Workup

  1. stirringstirring
  2. waitwas continued for 2.75 hours at room temperature
  3. stirringThen the reaction mixture was stirred
  4. temperatureat reflux temperature for 16 hours
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted twice with EtOAc
  7. dry with materialThe organic layers were dried over MgSO4
  8. filtrationfiltered
  9. additiontreated with silica gel
  10. customevaporated
  11. customThe product was purified by preparative HPLC (Gemini NX column)

Sources & evidence

ORD record
ord-b1ae53f629b34a92bdf4709a77bd1512
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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