Diethyl Ether → N-(4-methylphenyl)-4-methoxy-6-(3-methylphenoxy)-2-pyridine carboxamide

HRID 1250489Notes

Reaction equation

HRID 1250489 reaction equation
BrC1C=[C:6]([O:8][CH3:9])[CH:5]=[C:4](Br)[N:3]=1.[CH3:11][CH2:12][CH2:13][CH2:14][CH2:15]C.[Li]CCCC.[CH3:22][C:23]1[CH:28]=[CH:27][C:26]([N:29]=[C:30]=[O:31])=[CH:25][CH:24]=1.[CH2:32]([O:34][CH2:35][CH3:36])[CH3:33]>>[CH3:22][C:23]1[CH:28]=[CH:27][C:26]([NH:29][C:30]([C:4]2[CH:5]=[C:6]([O:8][CH3:9])[CH:33]=[C:32]([O:34][C:35]3[CH:11]=[CH:12][CH:13]=[C:14]([CH3:15])[CH:36]=3)[N:3]=2)=[O:31])=[CH:25][CH:24]=1

Participants

6

Reactant 5

HCID 3283Diethyl Ether2×HCID 8058HexaneHCID 693254-Methylphenyl isocyanateHCID 109015692,6-Dibromo-4-methoxypyridineHCID 178418339Butyllithium

Product 1

HCID 15906600N-(4-methylphenyl)-4-methoxy-6-(3-methylphenoxy)-2-pyridine carboxamide

Procedure

2.0 g (0.0075 mol) of 2,6-dibromo-4-methoxy pyridine was dissolved in about 30 ml of diethyl ether. While cooling the solution in a dry ice-acetone bath in an argon atmosphere, 6.0 ml of a 1.6M-hexane solution of BuLi (0.0075×1.3 mol) was added thereto, followed by stirring the solution for about 10 minutes. After 2.0 g (0.0075×2.0 mol) of 4-methyl phenyl isocyanate dissolved in about 5 ml of diethyl ether was added to the reaction solution, the solution was removed from the bath and stirred at room temperature for about 40 minutes. The reaction solution was mixed with about 10 ml of a 1.2N-aqueous hydrochloric acid solution, and then distributed in ethyl acetate-saturated sodium bicarbonate water, followed by washing with saturated brine. The organic phase of the obtained solution was dried with anhydrous sodium sulfate, concentrated and subjected to silica gel column chromatography (eluting solution: ethyl acetate/hexane) to separate a main fraction therefrom. The fraction was concentrated and then precipitated with hexane, thereby obtaining an aimed product.

Workup

  1. additionwas added
  2. additionwas added to the reaction solution
  3. customthe solution was removed from the bath
  4. stirringstirred at room temperature for about 40 minutes
  5. additionThe reaction solution was mixed with about 10 ml of a 1.2N-aqueous hydrochloric acid solution
  6. washby washing with saturated brine
  7. dry with materialThe organic phase of the obtained solution was dried with anhydrous sodium sulfate
  8. concentrationconcentrated
  9. washsubjected to silica gel column chromatography (eluting solution: ethyl acetate/hexane)
  10. customto separate a main fraction
  11. concentrationThe fraction was concentrated
  12. customprecipitated with hexane

Sources & evidence

ORD record
ord-f3d1561f1b0641c19d2120421bf84456
Source dataset
uspto-grants-2002_01
Patent number
US06339045B1

Reaction notes

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