Sodium Hydroxide → 3-(4-fluorophenyl)-5-methylisoxazole-4-carboxylic acid

HRID 1625924Notes

Reaction equation

HRID 1625924 reaction equation
C([O:3][C:4]([C:6]1[C:7]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[N:8][O:9][C:10]=1[CH3:11])=[O:5])C.[OH-].[Na+]>C(O)C.C1(C)C=CC=CC=1>[F:18][C:15]1[CH:14]=[CH:13][C:12]([C:7]2[C:6]([C:4]([OH:5])=[O:3])=[C:10]([CH3:11])[O:9][N:8]=2)=[CH:17][CH:16]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 22309061Ethyl 3-(4-fluorophenyl)-5-methyl-1,2-oxazole-4-carboxylate

Product 1

HCID 27807093-(4-fluorophenyl)-5-methylisoxazole-4-carboxylic acidYield 86%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of 179.5 g (0.72 mol) of 3-(4-Fluoro-phenyl)-5-methyl-isoxazole-4-carboxylic acid ethyl ester in 880 g of ethanol 95% was stirred at 20-30° C. for 40 minutes and then treated with 78.5 g of solid sodium hydroxide. The resulting mixture was stirred for 5 h at 20-30° C. Ethanol was removed in vacuum at 45-50° C. and the residue was subsequently treated with 500 g of water at 20-30° C. to afford a clear solution. The solution was stirred for 40 minutes and filtered. To the filtrate was added 235 g of methyl tert-butyl ether and 600 g of water and the resulting mixture stirred for 20 min and then stood for 20 min. The layers were separated and the aqueous layer was acidified to pH<1 with hydrochloric acid. The crystals were filtered and washed with water to provide 147 g crude wet product. The crude wet product was suspended in 680 g of toluene and the mixture was heated at 75-85° C. for 7 h. The mixture was cooled to 20-30° C. and stirred for 1 hour at this temperature. The crystals were filtered off and dried at 50-55° C. in vacuum over night to afford 137 g (86% yield) of the title acid as a white to slightly yellow solid with a purity of 99.9% (HPLC).

Workup

  1. stirringThe resulting mixture was stirred for 5 h at 20-30° C
  2. customEthanol was removed in vacuum at 45-50° C.
  3. additionthe residue was subsequently treated with 500 g of water at 20-30° C.
  4. customto afford a clear solution
  5. stirringThe solution was stirred for 40 minutes
  6. filtrationfiltered
  7. additionTo the filtrate was added 235 g of methyl tert-butyl ether and 600 g of water
  8. stirringthe resulting mixture stirred for 20 min
  9. waitstood for 20 min
  10. customThe layers were separated
  11. filtrationThe crystals were filtered
  12. washwashed with water
  13. customto provide 147 g crude wet product
  14. temperaturethe mixture was heated at 75-85° C. for 7 h
  15. temperatureThe mixture was cooled to 20-30° C.
  16. stirringstirred for 1 hour at this temperature
  17. filtrationThe crystals were filtered off
  18. customdried at 50-55° C. in vacuum over night

Sources & evidence

ORD record
ord-36cdca6bc7c140fe82ce355863bf0921
Source dataset
uspto-grants-2014_07
Patent number
US08785435B2

Reaction notes

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