Hydrochloric Acid → Cetirizine

HRID 1941198Notes

Reaction equation

HRID 1941198 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:10]2[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][O:18][CH2:19][C:20](N)=[O:21])[CH2:12][CH2:11]2)=[CH:5][CH:4]=1.[OH-:29].[Na+]>O>[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[N:10]2[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][O:18][CH2:19][C:20]([OH:29])=[O:21])[CH2:12][CH2:11]2)=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 14798Sodium HydroxideHCID 3068840Cetirizine amide

Product 1

HCID 2678CetirizineYield 80.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

26 ml of concentrated hydrochloric acid are added dropwise to a suspension of 25.2 g (0.065 mole) of dextrorotatory (+)-2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetamide (prepared at point 10 above) in 70 ml of water, causing the temperature of the mixture to rise to 38° C. The mixture is then heated at 50° C. for 17 hours. The reaction mixture is then cooled in an ice bath and the pH brought to a value of between 4 and 5 by addition of a 4N aqueous solution of sodium hydroxide. The resulting solution is extracted successively with 100 ml, then twice with 50 ml of dichloromethane. The organic phases are combined and dried over magnesium sulfate. They are filtered and the solvent is evaporated. The residual oil is dissolved in 243 ml of acetone and the solution is treated with 3.5 g of Norit and filtered through Celite, which is then washed with 35 ml of acetone. The solution is heated at reflux temperature and 198 ml (0.13 mole) of concentrated hydrochloric acid are added dropwise thereto. The mixture is cooled in an ice bath and allowed to stand for one hour. The precipitate which forms is filtered off, washed with 100 ml of acetone and dried under vacuum at 50° C. 24.1 g of the levorotatory dihydroshloride of 2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetic acid are obtained.

Workup

  1. customto rise to 38° C
  2. temperatureThe reaction mixture is then cooled in an ice bath
  3. extractionThe resulting solution is extracted successively with 100 ml
  4. dry with materialdried over magnesium sulfate
  5. filtrationThey are filtered
  6. customthe solvent is evaporated
  7. dissolutionThe residual oil is dissolved in 243 ml of acetone
  8. additionthe solution is treated with 3.5 g of Norit
  9. filtrationfiltered through Celite, which
  10. washis then washed with 35 ml of acetone
  11. temperatureThe solution is heated
  12. additionare added dropwise
  13. temperatureThe mixture is cooled in an ice bath
  14. filtrationThe precipitate which forms is filtered off
  15. washwashed with 100 ml of acetone
  16. customdried under vacuum at 50° C

Sources & evidence

ORD record
ord-ca17e950141a422082ad07fa609e020c
Source dataset
uspto-grants-1997_12
Patent number
US05703082

Reaction notes

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