Hydrochloric Acid → Fenofibric Acid

HRID 854507Notes

Reaction equation

HRID 854507 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 97.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
4 °C

Procedure

Fenofibrate (350. g, 0.970 mol) was suspended in 2 L of isopropanol. A solution of NaOH (77.6 g NaOH, 1.94 mol, 2 eq) in 1.8 L of water was added and the mixture heated to reflux for 2.7 hours. The solution was cooled to approximately 4° C. A solution of hydrochloric acid (697.2 g of a 10.03% solution, 69.90 g of HCl, 1.917 mol, 2 eq) was added maintaining the temperature at less than 5° C., and the product crystallized from solution. The crystallization can be optionally seeded with Form I fenofibric acid after approximately 50% of the hydrochloric acid is added. The slurry was warmed to 20° C. and mixed for 0.8 hours. The product was filtered, rinsed with 600 mL of 2:1 water:isopropanol, and then rinsed with 300 mL of water. The product was dried in a vacuum oven at 40° C. with a nitrogen purge for 14 hours, and then dried at 60° C. for 24 hours. The dry weight was 300.6 g, or 97.2% yield. 1H NMR (400 MHz, CD3OD) δ 7.72 (m, 2H), 7.71 (m, 2H), 7.52 (m, 2H), 6.95 (m, 2H), 1.66 (s, 6H); Anal. Calcd. for C17H15ClO4: C, 64.06; H, 4.74; N, Cl, 11.12. Found: C, 63.94; H, 4.64; Cl, 11.13.

Workup

  1. temperaturethe mixture heated
  2. temperatureto reflux for 2.7 hours
  3. temperaturemaintaining the temperature at less than 5° C.
  4. customthe product crystallized from solution
  5. customThe crystallization
  6. additionis added
  7. temperatureThe slurry was warmed to 20° C.
  8. additionmixed for 0.8 hours
  9. filtrationThe product was filtered
  10. washrinsed with 600 mL of 2:1 water
  11. washisopropanol, and then rinsed with 300 mL of water
  12. customThe product was dried in a vacuum oven at 40° C. with a nitrogen
  13. custompurge for 14 hours
  14. customdried at 60° C. for 24 hours

Sources & evidence

ORD record
ord-383a0196d52748978a53c16c74801563
Source dataset
uspto-grants-2007_08
Patent number
US07259186B2

Reaction notes

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