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Triethylamine → 3-(4-(2-isocyanatopropyl)phenyl)-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole

HRID 1772444
Notes
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Reaction equation

HRID 1772444 reaction equation
[CH3:1][CH:2]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:17]=[CH:16][N:15]([C:18]3[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:27])[F:26])=[CH:20][CH:19]=3)[N:14]=2)=[CH:9][CH:8]=1)C(O)=O.C([N:31]([CH2:34]C)CC)C.P(N=[N+]=[N-])(=O)(OC1C=CC=CC=1)[O:37]C1C=CC=CC=1>C1(C)C=CC=CC=1.C(OCC)(=O)C.O>[N:31]([CH:2]([CH3:1])[CH2:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]2[N:17]=[CH:16][N:15]([C:18]3[CH:19]=[CH:20][C:21]([O:24][C:25]([F:26])([F:27])[F:28])=[CH:22][CH:23]=3)[N:14]=2)=[CH:11][CH:12]=1)=[C:34]=[O:37]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 123414Diphenylphosphoryl azideHCID 904041342-methyl-3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)-propanoic acid

Product 1

HCID 904040983-(4-(2-isocyanatopropyl)phenyl)-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazoleYield 62%

Reagents, catalysts & solvents 3

HCID 962
Water
Solvent
HCID 1140TolueneSolvent
HCID 8857Ethyl AcetateSolvent

Procedure

To 2-methyl-3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)-propanoic acid (0.84 g, 2.2 mmol) in toluene (21.6 mL) was added triethylamine (0.33 mL, 2.4 mmol) and diphenyl phosphorazidate (0.47 mL, 2.2 mmol) and the solution was stirred at room temperature for 2 hours. The reaction was diluted with ethyl acetate and water and the layers separated. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude material was loaded onto a Celite® cartridge and purified by flash column chromatography using 0-100% ethyl acetate/B, where B=1:1 dichloromethane/hexanes, as eluent to afford the title compound as a white solid (0.53 g, 58%): 1H NMR (400 MHz, CDCl3) δ 8.56 (s, 1H), 8.21-8.11 (m, 2H), 7.88-7.77 (m, 2H), 7.39 (d, J=8.3 Hz, 2H), 7.32 (d, J=8.4 Hz, 2H), 3.94-3.80 (m, 1H), 2.87 (d, J=6.8 Hz, 2H), 1.35 (d, J=6.5 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ −58.03; ESIMS m/z 389 ([M+H]+).

Workup

  1. customthe layers separated
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified by flash column chromatography

Sources & evidence

ORD record
ord-2c8e71d4087a49178131e23e859d2832
Source dataset
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09249133B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes