Potassium Carbonate → Methyl 2-[2-[4-(4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorophenoxymethyl]-5-methylphen oxy]propionate

HRID 482387Notes

Reaction equation

HRID 482387 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:13](=[O:14])[N:12]([CH:15]([F:17])[F:16])[C:11]([CH3:18])=[N:10]1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:26][C:27]1[CH:39]=[CH:38][C:37]([CH3:40])=[CH:36][C:28]=1[O:29][CH:30]([CH3:35])[C:31]([O:33][CH3:34])=[O:32]>CN(C)C=O>[F:16][CH:15]([F:17])[N:12]1[C:13](=[O:14])[N:9]([C:3]2[CH:4]=[CH:5][C:6]([O:8][CH2:26][C:27]3[CH:39]=[CH:38][C:37]([CH3:40])=[CH:36][C:28]=3[O:29][CH:30]([CH3:35])[C:31]([O:33][CH3:34])=[O:32])=[CH:7][C:2]=2[F:1])[N:10]=[C:11]1[CH3:18]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 142799031-(2-Fluoro-4-hydroxyphenyl)-3-methyl-4-(difluoromethyl)-1H-1,2,4-triazol-5(4H)-oneHCID 15765398Methyl 2-(2-chloromethyl-5-methylphenoxy)propionate

Product 1

HCID 22904744Methyl 2-[2-[4-(4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorophenoxymethyl]-5-methylphen oxy]propionate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 0.50 g (0.0019 mole) of 1-(2-fluoro-4-hydroxyphenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one, 0.39 g (0.0028 mole) of anhydrous potassium carbonate, and 0.92 g (0.0038 mole) of methyl 2-(2-chloromethyl-5-methylphenoxy)propionate in 20 mL of N,N-dimethylformamide was heated at 90° C. for approximately 17 hours. At the end of this period the mixture was poured over ice, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water, dried over anhydrous magnesium sulfate, and filtered. The filtrate was evaporated under reduced pressure, leaving an orange oil as a residue. This oil was placed on a silica gel column and eluted first with methylene chloride and then with methylene chloride/ethyl acetate (97.5/2.5). After the product-containing fractions were combined and the solvents evaporated under reduced pressure, 0.82 g of 2-[2-[4-(4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorophenoxymethyl]-5-methylphenoxy]propionate was recovered as a yellow oil. The NMR and IR spectra were consistent with the proposed structure. NMR: 1.60 (d, 3H, JHH=8.0 Hz); 2.30 (s, 3H); 2.44 (s, 3H); 3.76 (s, 3H); 4.84 (q, 1H, JHH=8.0 Hz); 5.16 (dd, 2H, JHH=10.0 Hz); 6.56 (s, 1H); 6.78-7.32 (m, 6H).

Workup

  1. additionAt the end of this period the mixture was poured over ice
  2. extractionthe resulting mixture was extracted with ethyl acetate
  3. washThe extract was washed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customThe filtrate was evaporated under reduced pressure
  7. customleaving an orange oil as a residue
  8. washeluted first with methylene chloride
  9. customthe solvents evaporated under reduced pressure, 0.82 g of 2-[2-[4-(4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorophenoxymethyl]-5-methylphenoxy]propionate
  10. customwas recovered as a yellow oil

Sources & evidence

ORD record
ord-1a4a6d50a0134021bc8c9f442ff44fc4
Source dataset
uspto-grants-1998_08
Patent number
US05798316

Reaction notes

Loading…