Triethylamine → 3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)butanoyl azide

HRID 573846Notes

Reaction equation

HRID 573846 reaction equation
[F:1][C:2]([F:28])([F:27])[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]([CH3:26])[CH2:22][C:23]([OH:25])=O)=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1.C(N(CC)CC)C.P([N:52]=[N+:53]=[N-:54])(=O)(OC1C=CC=CC=1)OC1C=CC=CC=1>C1(C)C=CC=CC=1.C(OCC)(=O)C>[F:1][C:2]([F:28])([F:27])[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]([CH:21]([CH3:26])[CH2:22][C:23]([N:52]=[N+:53]=[N-:54])=[O:25])=[CH:17][CH:16]=3)=[N:11]2)=[CH:8][CH:9]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 123414Diphenylphosphoryl azideHCID 904054583-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)butanoic acid

Product 1

HCID 904042293-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)butanoyl azideYield 12%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 3-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)butanoic acid (C41) (1.77 g, 4.52 mmol) in toluene (18 mL) was added triethylamine (0.82 mL, 5.88 mol) and diphenyl phosphorazidate (1.05 mL, 4.98 mmol) and the solution was stirred at room temperature for 3 hours. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate. The organic layers were 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 clear oil (0.223 g, 12% yield): 1H NMR is consistent with a mixture of carbonyl azide and isocyanate. 1H NMR (400 MHz, CDCl3) δ 8.56 (s, 1H), 8.28-8.03 (m, 2H), 7.88-7.66 (m, 2H), 7.48-7.30 (m, 4H), 3.60-3.40 (m, 2H), 3.08 (q, J=6.9 Hz, 1H), 2.81-2.49 (m, 1H), 1.37 (dd, J=10.4, 7.0 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ −58.03; ESIMS m/z 417 ([M+H]+)

Workup

  1. washwashed with water
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. dry with materialThe organic layers were dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by flash column chromatography

Sources & evidence

ORD record
ord-c17405ec5c374ce285154ba1474d2b64
Source dataset
uspto-grants-2015_05
Patent number
US09029560B2

Reaction notes

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