Sodium hydride → 4-(3-Isopropyl-1,2,4-oxadiazol-5-YL)cyclohexan-1-one

HRID 1931578Notes

Reaction equation

HRID 1931578 reaction equation
[OH:1][NH:2][C:3](=[NH:7])[CH:4]([CH3:6])[CH3:5].[H-].[Na+].C(O[C:13]([CH:15]1[CH2:20][CH2:19][C:18](=[O:21])[CH2:17][CH2:16]1)=O)C>O1CCCC1>[CH:4]([C:3]1[N:7]=[C:13]([CH:15]2[CH2:20][CH2:19][C:18](=[O:21])[CH2:17][CH2:16]2)[O:1][N:2]=1)([CH3:6])[CH3:5]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 317638Ethyl 4-oxocyclohexanecarboxylateHCID 178449908HCID 178449908, compound2×

Product 1

HCID 579649554-(3-Isopropyl-1,2,4-oxadiazol-5-YL)cyclohexan-1-oneYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of N-hydroxy-isobutyramidine (Intermediate 8; 500 mg, 4.9 mmol) and 4 Å molecular sieves in tetrahydrofuran (15 mL) was stirred for 30 min at room temperature. Sodium hydride (60% dispersion; 204 mg, 5.1 mmol) was added and the mixture was heated to 60° C. for 20 min, and then cooled to room temperature. A solution of 4-oxo-cyclo-hexanecarboxylic acid ethyl ester (TCI America, Portland, Oreg., USA; 1.67 g, 9.8 mmol) in tetrahydrofuran (5 mL) was added. The reaction mixture was heated at reflux for 1 h and then cooled to room temperature and filtered. The solvent was evaporated and the residue was purified by flash chromatography, eluting with 1% methanol/dichloromethane to give 4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexanone (630 mg, 62%) as a white solid.

Workup

  1. temperaturethe mixture was heated to 60° C. for 20 min
  2. temperaturecooled to room temperature
  3. temperatureThe reaction mixture was heated
  4. temperatureat reflux for 1 h
  5. temperaturecooled to room temperature
  6. filtrationfiltered
  7. customThe solvent was evaporated
  8. customthe residue was purified by flash chromatography
  9. washeluting with 1% methanol/dichloromethane

Sources & evidence

ORD record
ord-f500569ab9444e4dbedd7cf3f62d7689
Source dataset
uspto-grants-2012_05
Patent number
US08188098B2

Reaction notes

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