2-Bromo-1-[2-(trifluoromethyl)phenyl]ethan-1-one → (2E)-3-(2-propan-2-ylphenyl)-2-[(Z)-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]methylidenehydrazinylidene]-4-[2-(trifluoromethyl)phenyl]-1,3-thiazolidin-4-ol

HRID 1404871Notes

Reaction equation

HRID 1404871 reaction equation
[CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[NH:10][C:11]([NH:13]/[N:14]=[CH:15]/[C:16]1[CH:21]=[CH:20][C:19]([C:22]2[N:26]=[CH:25][N:24]([C:27]3[CH:32]=[CH:31][C:30]([O:33][C:34]([F:37])([F:36])[F:35])=[CH:29][CH:28]=3)[N:23]=2)=[CH:18][CH:17]=1)=[S:12])([CH3:3])[CH3:2].[F:38][C:39]([F:51])([F:50])[C:40]1[CH:49]=[CH:48][CH:47]=[CH:46][C:41]=1[C:42](=[O:45])[CH2:43]Br>ClCCCl.C(OCC)(=O)C>[CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[N:10]1[C:42]([C:41]2[CH:46]=[CH:47][CH:48]=[CH:49][C:40]=2[C:39]([F:38])([F:50])[F:51])([OH:45])[CH2:43][S:12]/[C:11]/1=[N:13]/[N:14]=[CH:15]\[C:16]1[CH:17]=[CH:18][C:19]([C:22]2[N:26]=[CH:25][N:24]([C:27]3[CH:28]=[CH:29][C:30]([O:33][C:34]([F:37])([F:35])[F:36])=[CH:31][CH:32]=3)[N:23]=2)=[CH:20][CH:21]=1)([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 27784302-Bromo-1-[2-(trifluoromethyl)phenyl]ethan-1-oneHCID 885903141-(2-propan-2-ylphenyl)-3-[(E)-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]methylideneamino]thiourea

Product 1

HCID 140661991(2E)-3-(2-propan-2-ylphenyl)-2-[(Z)-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]methylidenehydrazinylidene]-4-[2-(trifluoromethyl)phenyl]-1,3-thiazolidin-4-olYield 38%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (E)-N-(2-isopropylphenyl)-2-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylidene)hydrazinecarbothioamide (0.30 g, 0.57 mmol) and 2-(trifluoromethyl)phenacyl bromide (0.22 g, 0.85 mmol) in DCE (30 mL) was heated to reflux and stirred overnight. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (100 mL), washed with water (2×50 mL), washed with brine solution (1×25 mL), and dried over anhydrous sodium sulfate. The solution was filtered, the filtrate concentrated, and the residue purified by flash chromatography (0-100% ethyl acetate/hexanes) to provide (Z)-3-(2-isopropylphenyl)-2-((E)-(4-(1-(4-(trifluoromethoxy)-phenyl)-1H-1,2,4-triazol-3-yl)benzylidene)hydrazono)-4-(2-(trifluoromethyl)-phenyl)thiazolidin-4-ol as a yellow solid (0.15 g, 38% yield): mp 115-117.5° C.; 1H NMR (400 MHz, CDCl3) δ 8.59 (s, 1H), 8.33 (s, 1H), 8.24 (d, J=8.4 Hz, 2H), 8.13 (s, 1H), 7.86-7.77 (m, 5H), 7.73 (d, J=7.2 Hz, 1H), 7.62 (dt, J=21.6, 7.2 Hz, 2H), 7.40 (d, J=8.2 Hz, 2H), 7.37-7.28 (m, 3H), 7.24-7.17 (m, 1H), 4.34 (s, 2H), 3.20 (dt, J=13.7, 6.8 Hz, 2H), 1.25 (d, J=6.9 Hz, 6H); 19F NMR (376 MHz, CDCl3) δ −57.99, −58.02; ESIMS m/z 711 ([M+H]+).

Workup

  1. temperatureto reflux
  2. washwashed with water (2×50 mL)
  3. washwashed with brine solution (1×25 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationThe solution was filtered
  6. concentrationthe filtrate concentrated
  7. customthe residue purified by flash chromatography (0-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-92dd5640062b48b6b5cdcfae9fcc1dc4
Source dataset
uspto-grants-2014_12
Patent number
US08916183B2

Reaction notes

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