Potassium Carbonate → Ciprofibrate

HRID 1605123Notes

Reaction equation

HRID 1605123 reaction equation
C(C1C=CC(OC(C)(C)C(O)=O)=CC=1)(=O)C.BrC(C)(C)C(OCC)=O.C(=O)([O-])[O-].[K+].[K+].[Cl:32][C:33]1([Cl:51])[CH2:35][CH:34]1[C:36]1[CH:50]=[CH:49][C:39]([O:40][C:41]([CH3:48])([CH3:47])[C:42]([O:44][CH2:45]C)=[O:43])=[CH:38][CH:37]=1.[OH-].[Na+]>C(#N)C>[Cl:32][C:33]1([Cl:51])[CH2:35][CH:34]1[C:36]1[CH:50]=[CH:49][C:39]([O:40][C:41]([CH3:48])([CH3:47])[C:42]([O:44][CH3:45])=[O:43])=[CH:38][CH:37]=1.[Cl:32][C:33]1([Cl:51])[CH2:35][CH:34]1[C:36]1[CH:50]=[CH:49][C:39]([O:40][C:41]([CH3:48])([CH3:47])[C:42]([OH:44])=[O:43])=[CH:38][CH:37]=1

Participants

8

Reactant 5

HCID 11430Potassium CarbonateHCID 11745Propanoic acid, 2-bromo-2-methyl-, ethyl ester2×HCID 14798Sodium HydroxideHCID 103600Ethyl 2-[4-(2,2-dichlorocyclopropyl)phenoxy]-2-methylpropionateHCID 1041062-(4-Acetylphenoxy)-2-methylpropionic acid

Product 2

HCID 2763CiprofibrateHCID 9944254Ciprofibrate Impurity D

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Alternatively, methyl 2-[p-(2,2-dichlorocyclopropyl)phenoxy]-2-methylpropionate was prepared from 20 g. of p-(2,2-dichlorocyclopropyl)phenol [Example 24, part (a)], 38 g. of ethyl 2-bromo-2-methylpropionate and 42 g. of potassium carbonate in 100 ml. of acetonitrile. The ethyl 2-bromo-2-methylpropionate was added in two equal portions, the second portion being added after seven hours of heating at reflux. The reaction mixture was heated at reflux for about three days and the product isolated to give 32 g. of ethyl 2-[p-(2,2-dichlorocyclopropyl)phenoxy]-2-methylpropionate. The latter was hydrolyzed in the usual manner with ethanolic sodium hydroxide to produce 2-[p-(2,2-dichlorocyclopropyl)phenoxy]-2-methylpropionic acid, identical with the compound formed in Example 24, part (b).

Workup

  1. additionthe second portion being added after seven hours
  2. temperatureof heating
  3. temperatureat reflux
  4. temperatureThe reaction mixture was heated
  5. temperatureat reflux for about three days
  6. customthe product isolated
  7. customto give 32 g

Sources & evidence

ORD record
ord-2c9e5d49e228447185367f2eb6f4eab1
Source dataset
uspto-grants-1976_04
Patent number
US03948973

Reaction notes

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