Phenol → Phenyl 2-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)cyclopropyl-carbamate

HRID 403188Notes

Reaction equation

HRID 403188 reaction equation
[F:1][C:2]([F:30])([F:29])[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]4[CH2:23][CH:22]4C(N=[N+]=[N-])=O)=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1.[C:31]1([OH:37])[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.CC[N:40]([CH2:43]C)CC.CC[O:47]C(C)=O>C1(C)C=CC=CC=1>[F:29][C:2]([F:30])([F:1])[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]4[CH2:23][CH:22]4[NH:40][C:43](=[O:47])[O:37][C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 996PhenolHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 866687332-{4-[1-(4-trifluoromethoxyphenyl)-1H-[1,2,4]triazol-3-yl]phenyl}cyclopropanecarbonyl azide

Product 1

HCID 68158463Phenyl 2-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)cyclopropyl-carbamateYield 72%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

2-{4-[1-(4-trifluoromethoxyphenyl)-1H-[1,2,4]triazol-3-yl]phenyl}cyclopropanecarbonyl azide (75 mg, 0.18 mmol, 1.0 equiv) was slurried in PhCH3 (0.52 mL, 0.35 M). Phenol (18.7 mg, 0.199 mmol, 1.1 equiv) was added, and the resulting mixture was heated at 100° C. for 2 h. During this time the slurry homogenized to give a yellow solution. The mixture was then cooled to 25° C. and Et3N (32.8 μL, 0.235 mmol, 1.3 equiv) was added. An off-white precipitate was observed to form. The mixture was diluted with 20% EtOAc in hexanes, and the product was collected by vacuum filtration to afford the title compound (62.9 mg, 72%) as an off-white solid: mp 171-173° C.; 1H NMR (400 MHz, CDCl3) δ 8.54 (s, 1H), 8.09 (d, J=8.3 Hz, 2H), 7.79 (d, J=9.0 Hz, 2H), 7.44-7.31 (m, 4H), 7.28 (d, J=7.7 Hz, 2H), 7.21 (t, J=7.4 Hz, 1H), 7.15 (d, J=7.9 Hz, 2H), 5.42 (s, 1H), 2.90 (s, 1H), 2.27 (ddd, J=9.6, 6.6, 3.2 Hz, 1H), 1.27-1.04 (m, 2H); ESIMS m/z 480 (M+H).

Workup

  1. customto give a yellow solution
  2. temperatureThe mixture was then cooled to 25° C.
  3. customto form
  4. filtrationthe product was collected by vacuum filtration

Sources & evidence

ORD record
ord-006cbb96d2db4aba8ddc4c2a276a91e2
Source dataset
uspto-grants-2014_06
Patent number
US08748340B2

Reaction notes

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