Methane → Cetirizine amide

HRID 2260812Notes

Reaction equation

HRID 2260812 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+].[I-].[K+].C>C1(C)C=CC=CC=1.CC1C=CC(C)=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

8

Reactant 5

HCID 297MethaneHCID 4875Potassium IodideHCID 9340NorchlorcyclizineHCID 10340Sodium CarbonateHCID 110189312-(2-Chloroethoxy)acetamide

Product 1

HCID 3068840Cetirizine amide

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 7809P-XyleneSolvent

Procedure

15 g (0.0523 mole) of dextrorotatory (+)-1-[(4-chlorophenyl)phenylmethyl]piperazine (prepared in Example 4.2), 8.3 g (0.0601 mole) of 2-(2-chloroethoxy)acetamide, 12.8 g (0.1203 mole) of sodium carbonate and 0.5 g (0.0030mole) of potassium iodide are added to a mixture of 100 ml of p-xylene and 150ml of toluene. The mixture is heated at reflux temperature for 17 hours. A small amount of Norit is added and the mixture is filtered while hot through Dicalite. The residue on the filter is washed with a small amount of toluene and the filtrate and washing solution are combined. The solvents are evaporated and the residue is taken up in 100 ml of toluene. The organic phase is washed successively with 100 ml of water and twice with 100 ml of a saturated aqueous solution of sodium chloride. The organic phase is separated off and the solvent evaporated. At this point, the crude residue obtained could be purified in a manner similar to that described at point 9 above, in order to obtain dextrorotatory (+)-2-[2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetamide in the form of the free base. However, if desired, the crude residue may also be converted to the corresponding dihydrochloride in the following manner : the crude residue obtained is taken up in 100 ml of acetone, cooled in an ice bath and 15 ml of concentrated hydrochloric acid are added dropwise thereto. A further 200 ml of acetone are added and the mixture is cooled and stirred on an ice bath for 1 hour. The precipitate is filtered off and dried under vacuum at 50° C. 19 g of the levorotatory dihydrochloride of 2-[2-[4-[(4-chlorophenyl) phenylmethyl-1-piperazinyl]ethoxy]acetamide are obtained.

Workup

  1. temperatureThe mixture is heated
  2. temperatureat reflux temperature for 17 hours
  3. filtrationthe mixture is filtered while hot through Dicalite
  4. washThe residue on the filter is washed with a small amount of toluene
  5. washthe filtrate and washing solution
  6. customThe solvents are evaporated
  7. washThe organic phase is washed successively with 100 ml of water and twice with 100 ml of a saturated aqueous solution of sodium chloride
  8. customThe organic phase is separated off
  9. customthe solvent evaporated
  10. customAt this point, the crude residue obtained could
  11. custombe purified in a manner similar to

Sources & evidence

ORD record
ord-667fed56c2dc433a8dde74b8eefd7ef6
Source dataset
uspto-grants-1995_12
Patent number
US05478941

Reaction notes

Loading…