Isopropanol → Fenofibrate

HRID 649356Notes

Reaction equation

HRID 649356 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)=[O:9])=[CH:4][CH:3]=1.Br[C:18]([CH3:23])([CH3:22])[C:19]([OH:21])=[O:20].C(=O)([O-])[O-].[K+].[K+].[CH:30](O)([CH3:32])[CH3:31]>O>[CH3:31][CH:30]([O:21][C:19]([C:18]([O:16][C:13]1[CH:12]=[CH:11][C:10]([C:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)=[O:9])=[CH:15][CH:14]=1)([CH3:23])[CH3:22])=[O:20])[CH3:32]

Participants

6

Reactant 4

HCID 3776IsopropanolHCID 11430Potassium CarbonateHCID 749242-Bromo-2-methylpropanoic acidHCID 1235044-Hydroxy-4'-chlorobenzophenone

Product 1

HCID 3339FenofibrateYield 77%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

100 g (0.43 mol) of (4-chlorophenyl)(4-hydroxyphenyl)methanone and 165 g (0.79 mol) of the 1-methylethyl ester of 2-bromo-2-methylpropanoic acid are introduced, under a nitrogen atmosphere, into a 3-necked round-bottomed flask equipped with a stirrer and a condenser. The reaction medium is heated to 110° C. and a solution of 50 g (0.36 mol) of potassium carbonate in 50 ml of demineralized water is then added slowly over a period of 20 minutes, with distillation taking place at 100° C. The distillate separates out into 2 phases. The lower phase is recycled into the reaction medium. After heating at 110°-112° C. for 1.5 h, the reaction medium is brought to 140° C. and a temperature of 140°-145° C. is maintained for 4 hours. The reaction medium is then cooled to about 90° C. and 210 ml of 80% isopropyl alcohol are added. The mixture is then left to cool for 12 h, with stirring, after which the suspension obtained is filtered at 0° C. The precipitate is washed with 4 times 200 ml of demineralized water and then recrystallized from propan-2-ol to give 119.5 g (yield=77%) of fenofibrate.

Workup

  1. customequipped with a stirrer and a condenser
  2. customat 100° C
  3. temperatureAfter heating at 110°-112° C. for 1.5 h
  4. customis brought to 140° C.
  5. temperaturea temperature of 140°-145° C. is maintained for 4 hours
  6. temperatureThe reaction medium is then cooled to about 90° C.
  7. waitThe mixture is then left
  8. temperatureto cool for 12 h
  9. customafter which the suspension obtained
  10. filtrationis filtered at 0° C
  11. washThe precipitate is washed with 4 times 200 ml of demineralized water
  12. customrecrystallized from propan-2-ol

Sources & evidence

ORD record
ord-5f02822089ed4f1ebf2f28104607bf56
Source dataset
uspto-grants-1988_04
Patent number
US04739101

Reaction notes

Loading…