Hydroxylamine → 3-(4-{4-Methyl-5-[2-(trifluoromethyl)phenyl]-4h-1,2,4-triazol-3-yl}bicyclo[2.2.2]oct-1-yl)-5-(4,4,4-trifluorobutyl)-1,2,4-oxadiazole

HRID 2079834Notes

Reaction equation

HRID 2079834 reaction equation
[CH3:1][N:2]1[C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[C:13]([F:16])([F:15])[F:14])=[N:5][N:4]=[C:3]1[C:17]12[CH2:24][CH2:23][C:20]([C:25]#[N:26])([CH2:21][CH2:22]1)[CH2:19][CH2:18]2.NO.[F:29][C:30]([F:38])([F:37])[CH2:31][CH2:32][CH2:33][C:34](O)=[O:35].C(N1C=CN=C1)([N:41]1C=CN=C1)=O>C(O)C.C(Cl)Cl>[CH3:1][N:2]1[C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[C:13]([F:14])([F:16])[F:15])=[N:5][N:4]=[C:3]1[C:17]12[CH2:22][CH2:21][C:20]([C:25]3[N:41]=[C:34]([CH2:33][CH2:32][CH2:31][C:30]([F:38])([F:37])[F:29])[O:35][N:26]=3)([CH2:23][CH2:24]1)[CH2:19][CH2:18]2

Participants

7

Reactant 4

HCID 787HydroxylamineHCID 682631,1'-CarbonyldiimidazoleHCID 27824465,5,5-trifluoropentanoic AcidHCID 671194154-(4-Methyl-5-(2-(trifluoromethyl)phenyl)-4H-1,2,4-triazol-3-yl)bicyclo[2.2.2]octane-1-carbonitrile

Product 1

HCID 166632793-(4-{4-Methyl-5-[2-(trifluoromethyl)phenyl]-4h-1,2,4-triazol-3-yl}bicyclo[2.2.2]oct-1-yl)-5-(4,4,4-trifluorobutyl)-1,2,4-oxadiazole

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of nitrile 1-F (0.56 g, 1.6 mmol) and hydroxylamine (50% aqueous, 4 ml) in ethanol (40 ml) was heated at 80° C. for 18 h. The resulting mixture was cooled to room temperature and concentrated in vacuo. The solid was stripped from toluene and dried under reduced pressure. A portion of the resulting white powder (0.050 g, 0.13 mmol) was added to a pre-stirred solution of 5,5,5-trifluoropentanoic acid (0.058 g, 0.37 mmol) and 1,1′-carbonyldiimidazole (0.050 g, 0.31 mmol) in methylene chloride (1 ml). The resulting mixture was stirred at room temperature for 24 h, then concentrated. The solid was resuspended in DMF and heated to 10° C. under a nitrogen atmosphere for 2 h. The crude product was purified by Gilson reverse phase chromatography eluting with a 10-90% CH3CN (0.1% TFA)/water (0.1% TFA) gradient. Solvent was removed in vacuo and the product free based from methylene chloride and saturated aqueous sodium bicarbonate. The organic layer was dried over MgSO4 and the solvent removed to yield 1-G as a white powder. MS (ESI+)=514.34 (M+1); 1H NMR (500 MHz, CDCl3): δ 7.86-7.83 (m, 1 H), 7.73-7.69 (m, 2 H), 7.56 (s, 1 H), 3.51 (s, 3 H), 2.99 (t, 2 H), 2.30-2.22 (m, 8 H), 2.17-2.09 (m, 8 H).

Workup

  1. concentrationconcentrated in vacuo
  2. customdried under reduced pressure
  3. concentrationconcentrated
  4. temperatureheated to 10° C. under a nitrogen atmosphere for 2 h
  5. customThe crude product was purified by Gilson reverse phase chromatography
  6. washeluting with a 10-90% CH3CN (0.1% TFA)/water (0.1% TFA) gradient
  7. customSolvent was removed in vacuo
  8. dry with materialThe organic layer was dried over MgSO4
  9. customthe solvent removed

Sources & evidence

ORD record
ord-a7a68d1165f84be7ae0d02b8016bba1c
Source dataset
uspto-grants-2011_04
Patent number
US07932280B2

Reaction notes

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