Hydrochloric Acid → Olopatadine Impurity 54

HRID 1196999Notes

Reaction equation

HRID 1196999 reaction equation
[CH3:1][N:2]([CH3:25])[CH2:3][CH2:4][CH:5]=[C:6]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[CH2:10][O:9][C:8]2[CH:17]=[CH:18][C:19]([C:21]([O:23]C)=[O:22])=[CH:20][C:7]1=2.CO.[OH-].[Na+].Cl>O>[CH3:25][N:2]([CH3:1])[CH2:3][CH2:4][CH:5]=[C:6]1[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[CH2:10][O:9][C:8]2[CH:17]=[CH:18][C:19]([C:21]([OH:23])=[O:22])=[CH:20][C:7]1=2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 53998201Methyl 11-(3-dimethylaminopropylidene)-6,11-dihydrodibenz[b,e]oxepin-2-carboxylate

Product 1

HCID 53645991Olopatadine Impurity 54Yield 99.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

In this example, 26.1 g of methyl 11-(3-dimethylaminopropylidene)-6,11-dihydrodibenz[b,e]oxepin-2-carboxylate is dissolved in a mixed solvent of 500 ml of methanol and 30 ml of water and 6.2 g of sodium hydroxide is added thereto. The mixture is heated at reflux for two hours. After allowing the mixture to stand for cooling, aqueous 4N-hydrochloric acid solution is added thereto to adjust the pH to 7 and the mixture is concentrated under reduced pressure. The concentrate is purified by column chromatography on high porous polymer (HP-20) (eluent: water:methanol=1:2) to obtain 25.0 g of the desired product.

Workup

  1. additionis added
  2. temperatureThe mixture is heated
  3. temperatureat reflux for two hours
  4. temperaturefor cooling
  5. concentrationthe mixture is concentrated under reduced pressure
  6. customThe concentrate is purified by column chromatography on high porous polymer (HP-20) (eluent: water:methanol=1:2)

Sources & evidence

ORD record
ord-1e76260c1fa24a6fab40a18ed039d313
Source dataset
uspto-grants-1992_05
Patent number
US05116863

Reaction notes

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