Dabco → (Z)-isopropyl 3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylate

HRID 508678Notes

Reaction equation

HRID 508678 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[CH:4]=[C:5]([C:13]2[N:17]=[CH:16][NH:15][N:14]=2)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C1N2CCN(CC2)C1.I/[CH:29]=[CH:30]\[C:31]([O:33][CH:34]([CH3:36])[CH3:35])=[O:32]>CN(C=O)C>[F:19][C:2]([F:1])([F:18])[C:3]1[CH:4]=[C:5]([C:13]2[N:17]=[CH:16][N:15](/[CH:29]=[CH:30]\[C:31]([O:33][CH:34]([CH3:36])[CH3:35])=[O:32])[N:14]=2)[CH:6]=[C:7]([C:9]([F:10])([F:12])[F:11])[CH:8]=1

Participants

5

Reactant 3

HCID 9237DabcoHCID 585036632-Propenoic acid, 3-iodo-, 1-methylethyl ester, (2Z)-HCID 178506083HCID 178506083, compound

Product 1

HCID 53386343(Z)-isopropyl 3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylateYield 61.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 2 L 3-neck round-bottom flask was charged with a solution of 3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazole (160 g) in DMF (960 mL) The solution was treated with DABCO (127.74 g, 2 eq.) and stirred for 30 min before adding (Z)-isopropyl 3-iodoacrylate (150.32 g, 1.1 eq.) dropwise. After 1 h, the reaction mixture was poured into an ice-water slurry (5 L) and extracted with EtOAc (3×1 L). The combined organic layers were washed with aqueous saturated sodium chloride solution (3×100 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure (35° C., 20 mmHg) to afford 250 g of the crude product that was purified by column chromatography (60/120 silica gel) using ethyl acetate/n-hexane gradient (the column was packed in hexane and the desired compound started eluting from 2% EtOAC/n-hexane). Fractions containing the desired compounds were combined to afford (Z)-isopropyl 3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylate (138 g, yield: 61%).

Workup

  1. waitAfter 1 h
  2. extractionextracted with EtOAc (3×1 L)
  3. washThe combined organic layers were washed with aqueous saturated sodium chloride solution (3×100 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure (35° C., 20 mmHg)
  7. customto afford 250 g of the crude product that
  8. customwas purified by column chromatography (60/120 silica gel)
  9. washthe desired compound started eluting from 2% EtOAC/n-hexane)
  10. additionFractions containing the desired compounds

Sources & evidence

ORD record
ord-300f54aaa3ea41bebfa84f0e52c40d8f
Source dataset
uspto-grants-2015_08
Patent number
US09096543B2

Reaction notes

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