Phenyl isocyanate → N-phenyl-4-methoxy-6-{3-(trifluoromethyl)phenoxy}-2-pyridine carboxamide

HRID 1250479Notes

Reaction equation

HRID 1250479 reaction equation
Br[C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)[N:3]=1.CCCCCC.C([Li])CCC.[C:32]1([N:38]=[C:39]=[O:40])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>C(OCC)C>[C:32]1([NH:38][C:39]([C:2]2[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([O:10][C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=3)[N:3]=2)=[O:40])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

6

Reactant 4

HCID 7672Phenyl isocyanateHCID 8058HexaneHCID 111318162-Bromo-4-methoxy-6-[3-(trifluoromethyl)phenoxy] pyridineHCID 178418339Butyllithium2×

Product 1

HCID 15906594N-phenyl-4-methoxy-6-{3-(trifluoromethyl)phenoxy}-2-pyridine carboxamide

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

1.0 g (0.0029 mol) of 2-bromo-4-methoxy-6-{3-(trifluoromethyl)phenoxy} pyridine was dissolved in about 15 ml of diethyl ether. The solution was cooled in a dry ice-acetone bath in an argon atmosphere and mixed with 1.9 ml of a 1.69M-hexane solution of n-butyl lithium (0.0029×1.1 mol; hereinafter referred to merely as “BuLi”), followed by stirring for about 10 minutes. After 0.86 g (0.0029×2.5 mol) of 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 30 minutes. The reaction solution was mixed with about 5 ml of 1.2N aqueous hydrochloric acid solution, and then distributed in ethyl acetate-water, followed by washing with saturated sodium bicarbonate water and 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 subjected to precipitation using hexane, thereby obtaining an aimed product.

Workup

  1. temperatureThe solution was cooled in a dry ice-acetone bath in an argon atmosphere
  2. additionwas added to the reaction solution
  3. customthe solution was removed from the bath
  4. stirringstirred at room temperature for about 30 minutes
  5. additionThe reaction solution was mixed with about 5 ml of 1.2N aqueous hydrochloric acid solution
  6. washby washing with saturated sodium bicarbonate water and 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. customsubjected to precipitation

Sources & evidence

ORD record
ord-d122f25dc58b4c72be0b54d4e3de1e63
Source dataset
uspto-grants-2002_01
Patent number
US06339045B1

Reaction notes

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