Sulfuric Acid → Fenofibrate

HRID 649354Notes

Reaction equation

HRID 649354 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+].S(=O)(=O)(O)O.[CH:35](O)([CH3:37])[CH3:36]>>[CH3:36][CH:35]([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])[CH3:37]

Participants

6

Reactant 5

HCID 1118Sulfuric AcidHCID 3776IsopropanolHCID 11430Potassium CarbonateHCID 749242-Bromo-2-methylpropanoic acidHCID 1235044-Hydroxy-4'-chlorobenzophenone

Product 1

HCID 3339FenofibrateYield 83.9%

Conditions

Temperature
120 °C

Procedure

465 g (2 mol) of (4-chlorophenyl)(4-hydroxyphenyl)methanone and 815 g (3.9 mol) of the 1-methylethyl ester of 2-bromo-2-methylpropanoic acid (alternative nomenclature: isopropyl 2-bromo-2-methylpropanoate) are introduced into a 4 liter reactor equipped with a stirrer and a condenser. The medium is heated to 120° C. and 265 g (1.92 mol) of potassium carbonate are then added with the aid of a funnel for solids. The reaction medium is subsequently heated for 5 hours at 140°-145° C. and then cooled to about 100° C. It is subsequently diluted with aqueous isopropyl alcohol and then acidified with sulfuric acid. The reaction medium is then cooled to 18°-20° C. in order to crystallize the product, which is filtered off and washed with sodium hydroxide solution and then water. The product is recrystallized from isopropanol to give 605 g of fenofibrate (yield=83.9%) with a purity greater than 99.5% (determination by high pressure liquid chromatography, abbreviated to HPLC).

Workup

  1. customequipped with a stirrer and a condenser
  2. temperatureThe reaction medium is subsequently heated for 5 hours at 140°-145° C.
  3. temperaturecooled to about 100° C
  4. temperatureThe reaction medium is then cooled to 18°-20° C. in order
  5. customto crystallize the product, which
  6. filtrationis filtered off
  7. washwashed with sodium hydroxide solution
  8. customThe product is recrystallized from isopropanol

Sources & evidence

ORD record
ord-e6b16daef47f499899eab172ba002cbf
Source dataset
uspto-grants-1988_04
Patent number
US04739101

Reaction notes

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