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

HRID 573827

Reaction equation

HRID 573827 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.C1C=CN=CC=1.O=S(=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

6

Reactant 3

HCID 8471TriethylamineHCID 168533Sulfur trioxide-pyridineHCID 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-c71bcca3fc7d4aa28d6d64cff59db85e
Source dataset
uspto-grants-2015_05
Patent number
US09029560B2

Linked notes

Loading…