Benzene → N-(ethoxymethyl)-4-methoxy-6-{3-(trifluoromethyl)phenoxy}-2-pyridine carboxamide

HRID 1250499Notes

Reaction equation

HRID 1250499 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[CH:11]=2)[N:6]=[C:5]([C:20]([NH2:22])=[O:21])[CH:4]=1.C1C=CC=CC=1.[H-].[Na+].[CH2:31]([O:33][CH2:34]Cl)[CH3:32]>C(OCC)(=O)C.CN(C=O)C>[CH2:31]([O:33][CH2:34][NH:22][C:20]([C:5]1[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=[C:7]([O:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([F:18])([F:19])[F:17])[CH:11]=2)[N:6]=1)=[O:21])[CH3:32]

Participants

7

Reactant 4

HCID 241BenzeneHCID 18523Chloromethyl ethyl etherHCID 24758Sodium hydrideHCID 183262294-Methoxy-6-{3-(trifluoromethyl)phenoxy}-2-pyridine carboxamide

Product 1

HCID 18326199N-(ethoxymethyl)-4-methoxy-6-{3-(trifluoromethyl)phenoxy}-2-pyridine carboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

1.0 g (0.0032 mol) of 4-methoxy-6-{3-(trifluoromethyl)phenoxy}-2-pyridine carboxamide was dissolved in a mixed solvent containing about 20 ml of benzene and about 10 ml of DMF, and the obtained solution was mixed with 0.14 g (ca. 60% in mineral oil; 0.0032×1.1 mol) of NaH, followed by treating the solution under reflux for several minutes. Thereafter, the resultant reaction solution was mixed with 0.61 g (0.0032×2.0 mol) of chloromethyl ethyl ether, followed by treating the solution under reflux for about 3 hours. The reaction solution was distributed in ethyl acetate-saturated sodium bicarbonate water and then washed with saturated brine. The organic phase of the solution was dried with anhydrous sodium sulfate, concentrated and purified by silica gel column chromatography (eluting solution: ethyl acetate/hexane), thereby obtaining an aimed product.

Workup

  1. additionby treating the solution
  2. temperatureunder reflux for several minutes
  3. customThereafter, the resultant reaction solution
  4. additionby treating the solution
  5. temperatureunder reflux for about 3 hours
  6. washwashed with saturated brine
  7. dry with materialThe organic phase of the solution was dried with anhydrous sodium sulfate
  8. concentrationconcentrated
  9. custompurified by silica gel column chromatography (eluting solution: ethyl acetate/hexane)

Sources & evidence

ORD record
ord-62b2204abffd4f3dad30fcadf711d46e
Source dataset
uspto-grants-2002_01
Patent number
US06339045B1

Reaction notes

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