Dabco → (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-1-(3,3-difluoroazetidin-1-yl)prop-2-en-1-one

HRID 1523355Notes

Reaction equation

HRID 1523355 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.[F:28][C:29]1([F:38])[CH2:32][N:31]([C:33](=[O:37])/[CH:34]=[CH:35]\I)[CH2:30]1.C(OCC)(=O)C.CCCCCC>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:35]=[CH:34]\[C:33]([N:31]3[CH2:32][C:29]([F:38])([F:28])[CH2:30]3)=[O:37])[N:14]=2)[CH:6]=[C:7]([C:9]([F:10])([F:12])[F:11])[CH:8]=1

Participants

6

Reactant 4

HCID 9237DabcoHCID 21226206Ethyl acetate hexaneHCID 86730374(Z)-1-(3,3-difluoroazetidin-1-yl)-3-iodoprop-2-en-1-oneHCID 178506083HCID 178506083, compound

Product 1

HCID 71496742(Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)-1-(3,3-difluoroazetidin-1-yl)prop-2-en-1-oneYield 25.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In a 25-mL, three-necked, round-bottomed flask equipped with nitrogen inlet, 3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazole (0.18 g, 1.0 eq.) was dissolved in DMF (5.0 mL, 27.0 V), and DABCO (0.143 g, 2.0 eq) and (Z)-1-(3,3-difluoroazetidin-1-yl)-3-iodoprop-2-en-1-one (0.192 g, 1.1 eq) were added. The reaction mixture was stirred at RT for 2-3 hr. The progress of the reaction was followed by TLC analysis on silica gel with 80% ethyl acetate-hexane as mobile phase, SM Rf=0.60 and Product Rf=0.4. Reaction mixture was poured in to ice water (50 mL) and extracted with EtOAc (3×25 mL). The combined organic layers were washed with brine solution (3×25 mL), dried over MgSO4, filtered, and concentrated by rotary evaporation (25° C., 20 mmHg) to afford 0.3 g of crude compound which was purified by column chromatography using silica 60/120 using ethyl acetate:hexane as mobile phase. The column (5×10 cm) was packed in hexane and started eluting in ethyl acetate in gradient manner starting with fraction collection (50-mL fractions) from 40% to 45% ethyl acetate in hexane. Compound started eluting with 40% ethyl acetate in hexane. Fractions containing such TLC profile were combined to obtain 70 mg of desired compound (yield 25.64%).

Workup

  1. customIn a 25-mL, three-necked, round-bottomed flask equipped with nitrogen inlet
  2. customReaction mixture
  3. extractionextracted with EtOAc (3×25 mL)
  4. washThe combined organic layers were washed with brine solution (3×25 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated by rotary evaporation (25° C., 20 mmHg)
  8. customto afford 0.3 g of crude compound which
  9. customwas purified by column chromatography
  10. washstarted eluting in ethyl acetate in gradient manner
  11. customstarting with fraction collection (50-mL fractions) from 40% to 45% ethyl acetate in hexane
  12. washCompound started eluting with 40% ethyl acetate in hexane
  13. additionFractions containing such TLC profile

Sources & evidence

ORD record
ord-e5b044dc585240dcb207cb4846fa591f
Source dataset
uspto-grants-2015_07
Patent number
US09079865B2

Reaction notes

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