Potassium Carbonate → Choline fenofibrate

HRID 2236328Notes

Reaction equation

HRID 2236328 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]([CH3:24])([CH3:23])[C:19]([O:21]C)=[O:20].C(=O)([O-])[O-].[K+].[K+].[OH-].[OH:32][CH2:33][CH2:34][N+:35]([CH3:38])([CH3:37])[CH3:36]>O>[OH:32][CH2:33][CH2:34][N+:35]([CH3:38])([CH3:37])[CH3:36].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([O:16][C:18]([CH3:24])([CH3:23])[C:19]([O-:21])=[O:20])=[CH:12][CH:11]=2)=[O:9])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 31255Choline, hydroxideHCID 90097Methyl 2-bromo-2-methylpropionateHCID 1235044-Hydroxy-4'-chlorobenzophenone

Product 1

HCID 11350701Choline fenofibrate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 100 g (0.43 mol) of (4-chlorophenyl)(4-hydroxyphenyl)-methanone and 148 g (0.82 mol) of methyl 2-bromo-2-methylpropanoate is prepared in a 1 l reactor maintained under a nitrogen atmosphere. The mixture is heated to 145° C., with thorough stirring, and 69 g (0.5 mol) of potassium carbonate are added. The reaction medium is maintained at 145° C. for 3 hours, with thorough stirring, during which time the water formed by the reaction is collected in the distillate. The pressure in the reactor is then gradually reduced in order to remove the excess brominated reactant by distillation. The mixture is then cooled to about 100° C. and 300 ml of n-propanol are added. The resulting mixture is stirred for 10 mm at 90° C. and then filtered at this temperature to remove the insoluble mineral salts. The residual solid is rinsed with 100 ml of hot n-propanol, which is combined with the previous filtrates. The solution obtained is placed in the 1 l reactor under a nitrogen atmosphere and 121.5 g (0.45 mol) of a 45% aqueous solution of choline hydroxide are added. The reaction mixture is stirred for 3 hours under gentle reflux of the solvent and about 240 ml of solvent are then distilled, 130 ml of n-propanol being added to the reactor. The reactor contents are subsequently filtered on a clarifying filter and then cooled slowly to about 15° C. The resulting suspension is filtered on an aspirator and the isolated solid is rinsed with 100 ml of cold n-propanol and then dried in a vacuum oven.

Workup

  1. customis prepared in a 1 l reactor
  2. temperaturemaintained under a nitrogen atmosphere
  3. additionare added
  4. customformed by the reaction
  5. distillationis collected in the distillate
  6. customto remove the excess brominated reactant
  7. distillationby distillation
  8. addition300 ml of n-propanol are added
  9. filtrationfiltered at this temperature
  10. customto remove the insoluble mineral salts
  11. washThe residual solid is rinsed with 100 ml of hot n-propanol, which
  12. customThe solution obtained
  13. stirringThe reaction mixture is stirred for 3 hours
  14. distillationare then distilled
  15. addition130 ml of n-propanol being added to the reactor
  16. filtrationThe reactor contents are subsequently filtered on a clarifying
  17. filtrationfilter
  18. temperaturecooled slowly to about 15° C
  19. filtrationThe resulting suspension is filtered on an aspirator
  20. washthe isolated solid is rinsed with 100 ml of cold n-propanol
  21. customdried in a vacuum oven

Sources & evidence

ORD record
ord-c8335b83c02e45a19362d7aa751be3c3
Source dataset
uspto-grants-2010_05
Patent number
US07714163B2

Reaction notes

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