Carbon Dioxide → Mofezolac

HRID 2286277Notes

Reaction equation

HRID 2286277 reaction equation
C([Li])CCC.[C:6](=[O:8])=[O:7].CC(C)=O.[CH3:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[C:25]([C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=3)=[C:24]([CH3:34])[O:23][N:22]=2)=[CH:17][CH:16]=1.C(=O)=O>C1COCC1>[CH3:13][O:14][C:15]1[CH:16]=[CH:17][C:18]([C:21]2[C:25]([C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=3)=[C:24]([CH2:34][C:6]([OH:8])=[O:7])[O:23][N:22]=2)=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 39549283,4-Bis(4-methoxyphenyl)-5-methylisoxazoleHCID 18522661Acetone cardiceHCID 178418339Butyllithium

Product 1

HCID 4237Mofezolac

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-75 °C

Procedure

n-Butyllithium (50 ml of 1.6 molar solution, 80 mmole) is added dropwise to a stirred, cold (dry-ice-acetone bath), solution of 3,4-di(p-methoxyphenyl)-5-methylisoxazol (21.72 g., 73.6 mmole, Ex. 2) in THF (220 ml) under a nitrogen atmosphere. After stirring for 1 hour at -75° C., the red coloured mixture is poured into crushed dry-ice and stirred. The stirred mixture is allowed to warm to room temperature, concentrated, and the residue dissolved in water. The resulting solution is twice extracted with ether, layered with ethyl acetate, cooled in ice and acidified with concentrated hydrochloric acid. The layers are separated and the aqueous layer extracted with ethyl acetate. The combined ethyl acetate layers are dried (MgSO4) and concentrated to give a sticky foam residue. Recrystallization from benzene gives the title compound as a colourless solid, m.p. 142°-143° C. The nmr (CDCl3) spectrum τ 6.2 (8H, s, d, CH3O and --CH2 --), 3.28 to 2.52 (8H, m, aryl H's), 0.45 (1H, broad, COOH) agrees with the assignment.

Workup

  1. additionis poured
  2. stirringstirred
  3. temperatureto warm to room temperature
  4. concentrationconcentrated
  5. dissolutionthe residue dissolved in water
  6. extractionThe resulting solution is twice extracted with ether
  7. temperaturecooled in ice
  8. customThe layers are separated
  9. extractionthe aqueous layer extracted with ethyl acetate
  10. dry with materialThe combined ethyl acetate layers are dried (MgSO4)
  11. concentrationconcentrated
  12. customto give a sticky foam residue
  13. customRecrystallization from benzene

Sources & evidence

ORD record
ord-b9fbfd279bf44af8ba761244478c0d4e
Source dataset
uspto-grants-1982_04
Patent number
US04327222

Reaction notes

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