Pyridine → 1-(4-{1-[4-(trifluoromethoxy)phenyl]-1H-1,2,4-triazol-3-yl}phenyl)ethan-1-one

HRID 924181

Reaction equation

HRID 924181 reaction equation
[F:1][C:2]([F:25])([F:24])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([CH:21]([OH:23])[CH3:22])=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1.C(N(CC)CC)C.N1C=CC=CC=1.S(=O)(=O)=O>ClCCl.CS(C)=O>[F:25][C:2]([F:1])([F:24])[O:3][C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21](=[O:23])[CH3:22])=[CH:17][CH:16]=3)=[N:11]2)=[CH:8][CH:9]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 8471TriethylamineHCID 24682Sulfur trioxideHCID 904038761-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)ethanol

Product 1

HCID 904043331-(4-{1-[4-(trifluoromethoxy)phenyl]-1H-1,2,4-triazol-3-yl}phenyl)ethan-1-oneYield 76.7%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To 1-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)ethanol (C24) (8.80 g, 25.2 mmol) in dichloromethane (168 mL) and dimethyl sulfoxide (84 mL) was added triethylamine (17 mL) and stirred in an ice bath. Pyridine.sulfur trioxide (16.0 g, 101 mmol) was added in two portions. The reaction was warmed to room temperature over 3 hours, diluted with dichloromethane, and washed with water. The aqueous layer was extracted one additional time with dichloromethane. The combined dichloromethane layers were washed with water, dried over anhydrous sodium sulfate, filtered, and adsorbed onto silica gel. Purification by flash column chromatography using 0-100% ethyl acetate/hexanes as eluent provided the title compound as a white solid (6.71 g, 73%): mp 140-141.5° C.; 1H NMR (400 MHz, CDCl3) δ 8.61 (s, 1H), 8.33-8.27 (m, 2H), 8.11-8.05 (m, 2H), 7.85-7.78 (m, 2H), 7.41 (dd, J=9.0, 0.8 Hz, 2H), 2.66 (s, 3H); 19F NMR (376 MHz, CDCl3) δ −58.01; ESIMS m/z 348 ([M+H]+).

Workup

  1. washwashed with water
  2. extractionThe aqueous layer was extracted one additional time with dichloromethane
  3. washThe combined dichloromethane layers were washed with water
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-5d3d2532e9f54fc38a75da54243b27d5
Source dataset
uspto-grants-2016_03
Patent number
US09278964B2

Linked notes

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