Hydrochloric Acid → Fenofibric Acid

HRID 854508Notes

Reaction equation

HRID 854508 reaction equation
CC([O:4][C:5]([C:7]([O:10][C:11]1[CH:12]=[CH:13][C:14]([C:17]([C:19]2[CH:20]=[CH:21][C:22]([Cl:25])=[CH:23][CH:24]=2)=[O:18])=[CH:15][CH:16]=1)([CH3:9])[CH3:8])=[O:6])C.[OH-].[Na+].Cl>C(O)(C)C.O>[CH3:9][C:7]([O:10][C:11]1[CH:12]=[CH:13][C:14]([C:17]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)=[O:18])=[CH:15][CH:16]=1)([C:5]([OH:6])=[O:4])[CH3:8]

Participants

6

Reactant 3

HCID 313Hydrochloric Acid2×HCID 3339FenofibrateHCID 14798Sodium Hydroxide

Product 1

HCID 64929Fenofibric AcidYield 96.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
75 °C

Procedure

Fenofibrate (200.0 g, 0.5543 mol) was suspended in 900 mL of isopropanol. A solution of NaOH (33.0 g NaOH, 0.825 mol, 1.49 eq) in 400 mL of water was added and the mixture heated to reflux for 2 hours. The solution was cooled to approximately 75° C. A solution of hydrochloric acid (652 g of a 5.0% solution, 32.8 g of HCl, 0.894 mol, 1.6 eq) was added maintaining the temperature above 55° C., and the product crystallized from solution. The slurry was cooled to 28° C. over 3.5 hours. The product was filtered and rinsed twice with 500 mL of water. The product was dried in a vacuum oven at 60° C. with a nitrogen purge for approximately 16 hours. The dry weight was 170.7 g, or 96.6% yield.

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux for 2 hours
  3. temperaturemaintaining the temperature above 55° C.
  4. customthe product crystallized from solution
  5. temperatureThe slurry was cooled to 28° C. over 3.5 hours
  6. filtrationThe product was filtered
  7. washrinsed twice with 500 mL of water
  8. customThe product was dried in a vacuum oven at 60° C. with a nitrogen
  9. custompurge for approximately 16 hours

Sources & evidence

ORD record
ord-cf58f6449bb341c688a7cf5d5632240b
Source dataset
uspto-grants-2007_08
Patent number
US07259186B2

Reaction notes

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