Sodium hydride → HCID 18338457, compound

HRID 2298422Notes

Reaction equation

HRID 2298422 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)[NH:9][CH:10]=1)=[O:5])[CH3:2].[H-].[Na+].Cl[C:24]1[CH:29]=[CH:28][N:27]=[C:26]([S:30][CH3:31])[N:25]=1>CN(C)C=O>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:19])([F:20])[F:18])[CH:12]=2)[N:9]([C:24]2[CH:29]=[CH:28][N:27]=[C:26]([S:30][CH3:31])[N:25]=2)[CH:10]=1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 971134-Chloro-2-methylthiopyrimidineHCID 178469885HCID 178469885, compound

Product 1

HCID 18338457HCID 18338457, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 2-(3-trifluoromethylphenyl)-1H-imidazole4-carboxylic acid ethyl ester (6.0 g, 0.0211 mol) in dimethyl formamide (60 mL) was added a 60% dispersion of sodium hydride in mineral oil (1.01 g, 0.0253 mol) and stirring was continued until noticeable H2 evolution stopped. 4-Chloro-2-methylthiopyrimidine (3.73 g, 0.0232 mol) was added dropwise and the reaction heated to 120° C. for 2 h and 140° C. overnight. The reaction was cooled and partitioned between H2O (300 mL) and ethyl acetate (300 mL). A small (30 mL) portion of 10% citric acid solution was added before the layers were shaken and separated. The ethyl acetate layer was dried over anhydrous magnesium sulfate and then concentrated to an oil which was chromatographed on silica using 15-35% ethyl acetate in hexanes to yield 6.43 g (75%) of the title compound as an oil.

Workup

  1. temperatureThe reaction was cooled
  2. custompartitioned between H2O (300 mL) and ethyl acetate (300 mL)
  3. additionA small (30 mL) portion of 10% citric acid solution was added before the layers
  4. stirringwere shaken
  5. customseparated
  6. dry with materialThe ethyl acetate layer was dried over anhydrous magnesium sulfate
  7. concentrationconcentrated to an oil which
  8. customwas chromatographed on silica using 15-35% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-3181914722d843d6aeab02dc95cf3d5b
Source dataset
uspto-grants-2002_12
Patent number
US06492516B1

Reaction notes

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