Hydrochloric Acid → 2-[1-(3-Methoxy-2-methylbenzyl)-2-cyclohexen-2-yl]-4,5-diphenyloxazole

HRID 1067133Notes

Reaction equation

HRID 1067133 reaction equation
[C:1]1([C:7]2[N:8]=[CH:9][O:10][C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li]CCCC.[CH3:23][O:24][C:25]1[C:26]([CH3:39])=[C:27]([CH:36]=[CH:37][CH:38]=1)[CH2:28][CH:29]1[CH2:34][CH2:33][CH2:32][CH2:31][C:30]1=O.Cl>C1COCC1>[CH3:23][O:24][C:25]1[C:26]([CH3:39])=[C:27]([CH:36]=[CH:37][CH:38]=1)[CH2:28][CH:29]1[CH2:34][CH2:33][CH2:32][CH:31]=[C:30]1[C:9]1[O:10][C:11]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:8]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6134984,5-DiphenyloxazoleHCID 183674192-(3-Methoxy-2-methylbenzyl)cyclohexanoneHCID 178418339Butyllithium

Product 1

HCID 183673122-[1-(3-Methoxy-2-methylbenzyl)-2-cyclohexen-2-yl]-4,5-diphenyloxazoleYield 67.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
5 °C

Procedure

To a solution of 4,5-diphenyloxazole (990 mg) in THF (15 ml) was added n-BuLi (1.56M solution in hexane, 2.87 ml) at −60° C. and stirred for 1 hour. To the mixture was added a solution of 2-(3-methoxy-2-methylbenzyl)cyclohexanone (945 mg) in THF (4 ml), warmed to 5° C., and stirred for 2 hours. To the reaction mixture was added 1N HCl and extracted with EtOAc. The organic layer was washed with water, saturated sodium hydrogen carbonate, water, and brine, dried over magnesium sulfate, evaporated in vacuo. The residue was dissolved in toluene (45 ml) and p-TsOH.H2O (79 mg) was added. The mixture was refluxed for 48 hours, cooled to room temperature, diluted with EtOAc, washed with saturated sodium hydrogen carbonate, water, and brine, dried over magnesium sulfate, evaporated in vacuo. The residue was purified by silica gel column chromatography (hexane-EtOAc 15:1 to 10:1) to give 2-[1-(3-methoxy-2-methylbenzyl)-2-cyclohexen-2-yl]-4,5-diphenyloxazole (1.19 g) as an amorphous solid.

Workup

  1. stirringstirred for 2 hours
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with water, saturated sodium hydrogen carbonate, water, and brine
  4. dry with materialdried over magnesium sulfate
  5. customevaporated in vacuo
  6. dissolutionThe residue was dissolved in toluene (45 ml)
  7. additionp-TsOH.H2O (79 mg) was added
  8. temperatureThe mixture was refluxed for 48 hours
  9. temperaturecooled to room temperature
  10. additiondiluted with EtOAc
  11. washwashed with saturated sodium hydrogen carbonate, water, and brine
  12. dry with materialdried over magnesium sulfate
  13. customevaporated in vacuo
  14. customThe residue was purified by silica gel column chromatography (hexane-EtOAc 15:1 to 10:1)

Sources & evidence

ORD record
ord-218e294cdbe140b6aae746033740c40a
Source dataset
uspto-grants-2001_06
Patent number
US06245790B1

Reaction notes

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