Acetone → Febuxostat

HRID 870885Notes

Reaction equation

HRID 870885 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].CC(C)=O.[OH-].[Na+].Cl>C(OCC)(=O)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

7

Reactant 4

HCID 180AcetoneHCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 98845495-Thiazolecarboxylic acid, 2-(3-cyano-4-(2-methylpropoxy)phenyl)-4-methyl-, ethyl ester

Product 1

HCID 134018FebuxostatYield 2.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

Ethyl 2-(3-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-carboxylate (50.0 g), acetone (500 mL), water (200 mL), and sodium hydroxide (6.96 g) 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., water (500 mL) and ethyl acetate (500 mL) were added, and the pH was adjusted to about 1 to 2 with hydrochloric acid (10.3 mL). The organic layer was separated and the aqueous layer was extracted into ethyl acetate (250 mL). The ethyl acetate layer was washed with water (300 mL). The ethyl acetate layer was distilled completely under vacuum below 60° C. The residue was dried at about 60° C. under vacuum to a constant weight to yield 1.0 g of the title compound. Purity by HPLC: 98.9%.

Workup

  1. temperatureheated to reflux
  2. temperatureThe mixture was maintained
  3. temperatureunder reflux until reaction completion
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted into ethyl acetate (250 mL)
  6. washThe ethyl acetate layer was washed with water (300 mL)
  7. distillationThe ethyl acetate layer was distilled completely under vacuum below 60° C
  8. customThe residue was dried at about 60° C. under vacuum to a constant weight

Sources & evidence

ORD record
ord-09a7848db7794e04a352488bcf3ae445
Source dataset
uspto-grants-2015_03
Patent number
US08969582B2

Reaction notes

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