Methyl iodide → 2-(2,4-Dichlorophenyl)-1-(N-methylcarbamoyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ol

HRID 728331Notes

Reaction equation

HRID 728331 reaction equation
[C:1]([CH2:4][C:5]([C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=1[Cl:20])([OH:12])[CH2:6][N:7]1[CH:11]=[N:10][CH:9]=[N:8]1)(=[O:3])[NH2:2].[H-].[Na+].[CH3:23]I>O1CCCC1>[Cl:20][C:14]1[CH:15]=[C:16]([Cl:19])[CH:17]=[CH:18][C:13]=1[C:5]([OH:12])([CH2:6][N:7]1[CH:11]=[N:10][CH:9]=[N:8]1)[CH2:4][C:1](=[O:3])[NH:2][CH3:23]

Participants

5

Reactant 3

HCID 6328Methyl iodide3×HCID 24758Sodium hydride3×HCID 136030731-Carbamoyl-2-(2,4-dichlorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ol

Product 1

HCID 198241592-(2,4-Dichlorophenyl)-1-(N-methylcarbamoyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1-Carbamoyl-2-(2,4-dichlorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-2-ol (1.0 g) was dissolved in dry tetrahydrofuran (20 ml) and the reaction mixture was cooled to 0°-5° C. Sodium hydride (0.15 g, as a 50% dispersion in oil) was then added, the mixture stirred for 10 minutes and methyl iodide (0.45 g) added. Further quantities of methyl iodide (90 mg) and sodium hydride (375 mg, as a 50% dispersion in oil) were added. After stirring for a few minutes, yet further quantities of methyl iodide (90 mg) and sodium hydride (375 mg, as a 50% dispersion in oil) were added. The mixture was then quenched in water and extracted with ethyl acetate (3×50 ml). The combined organic extracts were dried (MgSO4) and evaporated to give the crude product as a gum. A solution of this gum in methylene chloride (20 ml) was chromatographed on a silica gel column (10 g), eluting with methylene chloride (100 ml), then with methylene chloride containing 2% isopropanol and 0.2% NH4OH (300 ml), and finally with methylene chloride containing 5% isopropanol and 0.5% NH4OH (500 ml). Appropriate fractions were collected to yield the title compound, which was recrystallized from cyclohexane (yield 41 mg, m.p. 151°-154° C.).

Workup

  1. temperaturethe reaction mixture was cooled to 0°-5° C
  2. stirringAfter stirring for a few minutes
  3. customThe mixture was then quenched in water
  4. extractionextracted with ethyl acetate (3×50 ml)
  5. dry with materialThe combined organic extracts were dried (MgSO4)
  6. customevaporated
  7. customto give the crude product as a gum
  8. customA solution of this gum in methylene chloride (20 ml) was chromatographed on a silica gel column (10 g)
  9. washeluting with methylene chloride (100 ml)
  10. customAppropriate fractions were collected

Sources & evidence

ORD record
ord-74d819fe210341639114e643c101d33c
Source dataset
uspto-grants-1991_09
Patent number
US05047548

Reaction notes

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