Toluene → (E)-ethyl 2-methyl-3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)acrylate

HRID 573840Notes

Reaction equation

HRID 573840 reaction equation
[F:1][C:2]([F:24])([F:23])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:22]=[CH:21][C:18](C=O)=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1.C1(P(C2C=CC=CC=2)(C2C=CC=CC=2)=[C:32]([CH3:38])[C:33]([O:35][CH2:36][CH3:37])=[O:34])C=CC=CC=1.[C:51]1(C)C=CC=CC=1>>[CH3:51]/[C:32](=[CH:38]\[C:18]1[CH:21]=[CH:22][C:15]([C:12]2[N:13]=[CH:14][N:10]([C:7]3[CH:6]=[CH:5][C:4]([O:3][C:2]([F:1])([F:24])[F:23])=[CH:9][CH:8]=3)[N:11]=2)=[CH:16][CH:17]=1)/[C:33]([O:35][CH2:36][CH3:37])=[O:34]

Participants

4

Reactant 3

HCID 1140TolueneHCID 79792Ethyl 2-(triphenylphosphoranylidene)propionate2×HCID 578244624-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzaldehyde

Product 1

HCID 90438205(E)-ethyl 2-methyl-3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)acrylateYield 62%

Conditions

Temperature
110 °C

Procedure

4-(1-(4-(Trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzaldehyde (7.56 g, 22.7 mmol) and ethyl 2-(triphenylphosphoranylidene)propanoate (9.87 g, 27.2 mmol) in anhydrous toluene (30 mL) was heated at 110° C. for 16 hours. Additional ethyl 2-(triphenylphosphoranylidene)propanoate (2.40 g, 6.06 mmol) was then added, and the reaction was heated at 110° C. for 4 hours. The reaction was cooled, concentrated under vacuum, and loaded onto silica gel. Purification by flash column chromatography using 0-100% ethyl acetate/hexanes as eluent followed by reverse-phase flash column chromatography using 0-100% acetonitrile/water as eluent afforded the title compound as a white solid (5.92 g, 62%): mp 126-127.5° C.; 1H NMR (400 MHz, CDCl3) δ 8.58 (s, 1H), 8.27-8.17 (m, 2H), 7.84-7.78 (m, 2H), 7.73 (s, 1H), 7.52 (d, J=8.2 Hz, 2H), 7.40 (d, J=8.3 Hz, 2H), 4.29 (q, J=7.1 Hz, 2H), 2.17 (d, J=1.5 Hz, 3H), 1.37 (t, J=7.1 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ −58.02; ESIMS m/z 418 ([M+H]+).

Workup

  1. temperatureThe reaction was cooled
  2. concentrationconcentrated under vacuum
  3. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-bfdbc201b0c74c3490f4596144987236
Source dataset
uspto-grants-2015_05
Patent number
US09029560B2

Reaction notes

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