Hydrochloric Acid → Febuxostat

HRID 870884Notes

Reaction equation

HRID 870884 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:14]2[S:15][C:16]([C:20]([O:22]CC)=[O:21])=[C:17]([CH3:19])[N:18]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][CH:11]([CH3:13])[CH3:12])#[N:2].[OH-].[Na+].Cl>CC(C)=O>[CH3:19][C:17]1[N:18]=[C:14]([C:5]2[CH:6]=[CH:7][C:8]([O:9][CH2:10][CH:11]([CH3:13])[CH3:12])=[C:3]([C:1]#[N:2])[CH:4]=2)[S:15][C:16]=1[C:20]([OH:22])=[O:21]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 98845495-Thiazolecarboxylic acid, 2-(3-cyano-4-(2-methylpropoxy)phenyl)-4-methyl-, ethyl ester

Product 1

HCID 134018FebuxostatYield 36.3%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
25 °C

Procedure

Ethyl 2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-carboxylate (3.0 g), acetone (30 mL), and 1 N sodium hydroxide solution (12 mL) were placed into a round bottom flask and heated to reflux. The mixture was maintained under reflux until reaction completion. After the reaction was completed, the mass was cooled to about 25° C. and the pH was adjusted to about 1 to 2 with hydrochloric acid (1.5 mL). The mass was extracted into ethyl acetate (40 mL). The ethyl acetate layer was washed with water (30 mL). The ethyl acetate layer was distilled completely under vacuum below 60° C. Acetone (30 mL) was added to the residue and the mixture was heated to reflux and maintained for about 30 minutes. The mass was then cooled to about 25° C., maintained for about 60 minutes, filtered under vacuum and the solid was washed with acetone (3 mL). The wet solid was dried at about 60° C. to a constant weight to yield 1.0 g of the title compound. Purity by HPLC: 99.5%.

Workup

  1. temperatureheated to reflux
  2. temperatureThe mixture was maintained
  3. temperatureunder reflux until reaction completion
  4. extractionThe mass was extracted into ethyl acetate (40 mL)
  5. washThe ethyl acetate layer was washed with water (30 mL)
  6. distillationThe ethyl acetate layer was distilled completely under vacuum below 60° C
  7. additionAcetone (30 mL) was added to the residue
  8. temperaturethe mixture was heated
  9. temperatureto reflux
  10. temperaturemaintained for about 30 minutes
  11. temperatureThe mass was then cooled to about 25° C.
  12. temperaturemaintained for about 60 minutes
  13. filtrationfiltered under vacuum
  14. washthe solid was washed with acetone (3 mL)
  15. customThe wet solid was dried at about 60° C. to a constant weight

Sources & evidence

ORD record
ord-254278f0d92e4418a655aea7239bf430
Source dataset
uspto-grants-2015_03
Patent number
US08969582B2

Reaction notes

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