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

HRID 1250481Notes

Reaction equation

HRID 1250481 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]([O:17][C:18]([F:21])([F:20])[F:19])[CH:12]=2)[N:3]=1.CCCCCC.[Li]CCCC.[C:33]1([N:39]=[C:40]=[O:41])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>C(OCC)C>[C:33]1([NH:39][C:40]([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]([O:17][C:18]([F:21])([F:20])[F:19])[CH:12]=3)[N:3]=2)=[O:41])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

6

Reactant 4

HCID 7672Phenyl isocyanateHCID 8058HexaneHCID 541394232-Bromo-4-methoxy-6-{3-(trifluoromethoxy)phenoxy} pyridineHCID 178418339Butyllithium

Product 1

HCID 15906599N-phenyl-4-methoxy-6-{3-(trifluoromethoxy)phenoxy}-2-pyridine carboxamide

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

1.0 g (0.0027 mol) of 2-bromo-4-methoxy-6-{3-(trifluoromethoxy)phenoxy} pyridine was dissolved in about 15 ml of diethyl ether. The obtained solution was cooled in a dry ice-acetone bath in an argon atmosphere and mixed with 2.6 ml of a 1.6M-hexane solution of BuLi (0.0027×1.5 mol), followed by stirring for about 10 minutes. After 0.74 g (0.0027×2.3 mol) of phenyl isocyanate dissolved in about 5 ml of diethyl ether was added to the reaction solution, the obtained solution was removed from the bath and stirred at room temperature for about 45 minutes. The reaction solution was mixed with about 5 ml of a 1.2N-aqueous hydrochloric acid solution, and then distributed in ethyl acetate-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 obtained fraction was concentrated and then subjected to precipitation using hexane, thereby obtaining an aimed product.

Workup

  1. temperatureThe obtained solution was cooled in a dry ice-acetone bath in an argon atmosphere
  2. additionwas added to the reaction solution
  3. customthe obtained solution was removed from the bath
  4. stirringstirred at room temperature for about 45 minutes
  5. additionThe reaction solution was mixed with about 5 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 obtained fraction was concentrated
  12. customsubjected to precipitation

Sources & evidence

ORD record
ord-97550dd87757431a9a691d0854cbd5d4
Source dataset
uspto-grants-2002_01
Patent number
US06339045B1

Reaction notes

Loading…