N'-Hydroxy-4-methylbenzenecarboximidamide → 5-(3-Tert-butyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-7-yl)-3-(p-tolyl)-1,2,4-oxadiazole

HRID 2047646Notes

Reaction equation

HRID 2047646 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][C:5]([C:6](=[N:8][OH:9])[NH2:7])=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].[C:18]([C:22]1[N:26]2[CH2:27][CH2:28][CH:29]([C:31](OCC)=O)[CH2:30][C:25]2=[N:24][N:23]=1)([CH3:21])([CH3:20])[CH3:19].C(=O)(O)[O-].[Na+]>O1CCCC1.C(OCC)(=O)C>[C:18]([C:22]1[N:26]2[CH2:27][CH2:28][CH:29]([C:31]3[O:9][N:8]=[C:6]([C:5]4[CH:4]=[CH:3][C:2]([CH3:1])=[CH:11][CH:10]=4)[N:7]=3)[CH2:30][C:25]2=[N:24][N:23]=1)([CH3:21])([CH3:19])[CH3:20]

Participants

7

Reactant 4

HCID 209113N'-Hydroxy-4-methylbenzenecarboximidamideHCID 516892Sodium BicarbonateHCID 23665647Potassium tert-butoxideHCID 67300535Ethyl 3-t-butyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-7-carboxylate

Product 1

HCID 673002765-(3-Tert-butyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-7-yl)-3-(p-tolyl)-1,2,4-oxadiazoleYield 49%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Add 4-methylbenzamidoxime (1.44 g, 9.3 mmol) to a 1M solution of potassium tert-butoxide (8.6 mL, 8.6 mmol) diluted with tetrahydrofuran (120 mL). Add ethyl 3-t-butyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-7-carboxylate (2.0 g, 7.2 mmol) and stir overnight at room temperature. Dissolve the reaction in a 1:1 mixture of half saturated aqueous sodium bicarbonate and ethyl acetate. Separate the phases and extract the aqueous phase with ethyl acetate. Wash the combined organic layers with aqueous saturated sodium chloride, dry over anhydrous sodium sulfate, filter, and concentrate under reduced pressure. Purify the resulting residue by silica gel flash chromatography eluting with 25-100% ethyl acetate:hexane followed by 5% methanol:ethyl acetate. Recrystallize from dichloromethane and hexane to afford the title compound as a white solid (1.19 g). 1H NMR (CDCl3) δ 1.46 (s, 9H), 2.4 (s, 4H), 2.59 (m, 1H), 3.4 (m, 1H), 3.54-3.69 (m, 2H), 4.11 (m, 1H), 4.38 (m, 1H), 7.22-7.33 (m, 2H), 7.9-7.98 (m, 2H).

Workup

  1. dissolutionDissolve
  2. customthe reaction
  3. customSeparate the phases
  4. extractionextract the aqueous phase with ethyl acetate
  5. washWash the combined organic layers with aqueous saturated sodium chloride
  6. dry with materialdry over anhydrous sodium sulfate
  7. filtrationfilter
  8. concentrationconcentrate under reduced pressure
  9. customPurify the resulting residue by silica gel flash chromatography
  10. washeluting with 25-100% ethyl acetate
  11. customRecrystallize from dichloromethane and hexane

Sources & evidence

ORD record
ord-ce5642a54e914473b03af3b7a4d38967
Source dataset
uspto-grants-2013_11
Patent number
US08592590B2

Reaction notes

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