Methane → Cetirizine amide

HRID 2304466Notes

Reaction equation

HRID 2304466 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[N:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:4][CH:3]=1.Cl[CH2:22][CH2:23][O:24][CH2:25][C:26]([NH2:28])=[O:27].C(=O)([O-])[O-].[Na+].[Na+].C>[I-].[K+].C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:9]2[CH2:10][CH2:11][N:12]([CH2:22][CH2:23][O:24][CH2:25][C:26]([NH2:28])=[O:27])[CH2:13][CH2:14]2)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 297MethaneHCID 9340NorchlorcyclizineHCID 10340Sodium CarbonateHCID 110189312-(2-Chloroethoxy)acetamide

Product 1

HCID 3068840Cetirizine amideYield 79.6%

Reagents, catalysts & solvents 2

HCID 4875Potassium IodideCatalystHCID 1140TolueneSolvent

Procedure

77 g (0.2685 mole) of levorotatory (−)-1-[(4-chlorophenyl)phenylmethyl]piperazine (prepared in Example 4.1), 40.5 g (0.2932 mole) of 2-(2-chloroethoxy)acetamide, 62.8 g (0.591 mole) of sodium carbonate and 2 g (0.0120 mole) of potassium iodide are added to 700 ml of toluene. The mixture is heated at reflux temperature for 24 hours. 10 g of Norit are then added and the mixture is filtered while hot through Dicalite. The filtrate is washed with 500 ml of water and then with 500 ml of a saturated aqueous solution of sodium chloride. The organic phase is separated and dried over 250 g of sodium sulfate. It is then filtered and the solvent is evaporated. The residual oil is taken up in 1500 ml of hot diisopropyl oxide. The solution is heated under reflux and allowed to crystallize by cooling in an ice bath. The crystals are filtered, washed with a small amount of diisopropyl oxide and dried under vacuum at 40° C. 82.91 g of levorotatory (−)-2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetamide are obtained.

Workup

  1. temperatureThe mixture is heated
  2. temperatureat reflux temperature for 24 hours
  3. filtrationthe mixture is filtered while hot through Dicalite
  4. washThe filtrate is washed with 500 ml of water
  5. customThe organic phase is separated
  6. dry with materialdried over 250 g of sodium sulfate
  7. filtrationIt is then filtered
  8. customthe solvent is evaporated
  9. temperatureThe solution is heated
  10. temperatureunder reflux
  11. customto crystallize
  12. temperatureby cooling in an ice bath
  13. filtrationThe crystals are filtered
  14. washwashed with a small amount of diisopropyl oxide
  15. customdried under vacuum at 40° C

Sources & evidence

ORD record
ord-9aae64f7557648ef900b4b574de3d1cf
Source dataset
uspto-grants-2002_08
Patent number
US06436942B1

Reaction notes

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