Acetylacetone → 1-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)propan-2-one

HRID 1772544Notes

Reaction equation

HRID 1772544 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[CH:11][N:10]([C:13]3[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=3)[N:9]=2)=[CH:4][CH:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC(=O)[CH2:34][C:35](=[O:37])[CH3:36]>CS(C)=O.[Cu]I>[F:21][C:20]([F:23])([F:22])[O:19][C:16]1[CH:17]=[CH:18][C:13]([N:10]2[CH:11]=[N:12][C:8]([C:5]3[CH:6]=[CH:7][C:2]([CH2:34][C:35](=[O:37])[CH3:36])=[CH:3][CH:4]=3)=[N:9]2)=[CH:14][CH:15]=1

Participants

6

Reactant 3

HCID 31261AcetylacetoneHCID 62657Potassium Phosphate, TribasicHCID 904040773-(4-bromophenyl)-1-(4-(trifluoromethoxy)phenyl)-1 H-1,2,4-triazole

Product 1

HCID 904125151-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)propan-2-oneYield 35.3%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
110 °C

Procedure

3-(4-Bromophenyl)-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (C52) (11 g, 29 mmol), copper(I) iodide (0.55 g, 2.9 mmol), potassium phosphate (18 g, 86 mmol), and pentane-2,4-dione (8.9 mL, 86 mmol) were dissolved in dimethylsulfoxide (120 mL) in a 500 mL round bottomed flask. The reaction was heated at 110° C. for 19 hours. The solution was cooled to room temperature and then quenched with hydrogen chloride (2 N). The excess base was removed by gravity filtration and the filtrate was extracted with ethyl acetate. The organics were washed with water, extracted, dried, and concentrated. Purification by flash column chromatography using 0-30% ethyl acetate/hexanes afforded the title compound as a pure orange solid (3.7 g, 35%): 1H NMR (400 MHz, CDCl3) δ 8.56 (s, 1H), 8.17 (d, J=8.2 Hz, 2H), 7.80 (d, J=9.0 Hz, 2H), 7.39 (dt, J=8.1, 1.0 Hz, 2H), 7.33 (dd, J=8.1, 0.6 Hz, 2H), 3.76 (s, 2H), 2.19 (s, 3H); ESIMS m/z 361 ([M]+).

Workup

  1. temperatureThe solution was cooled to room temperature
  2. customquenched with hydrogen chloride (2 N)
  3. customThe excess base was removed by gravity filtration
  4. extractionthe filtrate was extracted with ethyl acetate
  5. washThe organics were washed with water
  6. extractionextracted
  7. customdried
  8. concentrationconcentrated
  9. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-de651c02c89145528d881ef26a05a83c
Source dataset
uspto-grants-2016_02
Patent number
US09249133B2

Reaction notes

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