Sodium Carbonate → HCID 18328707, compound

HRID 1249670Notes

Reaction equation

HRID 1249670 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[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:22][CH2:23][CH2:24][O:25][CH2:26][C:27]([NH2:29])=[O:28].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C(C)=CC=CC=1>[ClH:22].[ClH:22].[F:21][C:18]1[CH:19]=[CH:20][C:15]([CH:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[N:9]2[CH2:10][CH2:11][N:12]([CH2:23][CH2:24][O:25][CH2:26][C:27]([NH2:29])=[O:28])[CH2:13][CH2:14]2)=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 1529321-(Bis(4-fluorophenyl)methyl)piperazineHCID 110189312-(2-Chloroethoxy)acetamide

Product 1

HCID 18328707HCID 18328707, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Conditions

Temperature
140 °C

Procedure

A suspension of 11.0 g (0.038 mol) of 1-[bis(4-fluorophenyl)methyl]-piperazine, 10.5 g (0.076 mol) of 2-(2-chlorethoxy)acetamide and 8.1 g of anhydrous sodium carbonate in 40 ml of xylene is heated under reflux at 140° C. for 4 hours. The precipitate which forms is filtered off and then washed with toluene. The filtrate and toluene used for washing are combined. The resulting organic phase is extracted with 80 ml of 1N aqueous hydrochloride acid, and the aqueous phase is washed twice with toluene. Toluene is added to the resulting aqueous phase, then 80 ml of 1N aqueous sodium hydroxyde solution are added, and the aqueous mixture is extracted once with toluene. The organic phase is washed once with water, dried over anhydrous sodium sulphate and the solvents are evaporated off with a rotative evaporator until dryness. At this stage, the evaporation residue consists of 2-[4-[bis(4-fluorophenyl)methyl]-1-piperazinyl]ethoxyacetamide, which may be converted into its dihydrochloride salt as follows: the evaporation residue is taken up with 50 ml isopropanol and filtered; a 4.38 N alcoholic hydrochloric acid solution (17.5 ml) is added to the isopropanol solution and the mixture is allowed to crystallize. The precipitate is filtered, washed with isopropanol and diethyl ether, then dried in vacuo. This way, 15.8 g (90%) 2-[4-[bis(4-fluorophenyl)methyl]-1-piperazinyl]ethoxyacetamide dihydrochloride are obtained.

Workup

  1. temperatureis heated
  2. filtrationThe precipitate which forms is filtered off
  3. washwashed with toluene
  4. washfor washing
  5. extractionThe resulting organic phase is extracted with 80 ml of 1N aqueous hydrochloride acid
  6. washthe aqueous phase is washed twice with toluene
  7. additionToluene is added to the resulting aqueous phase
  8. addition80 ml of 1N aqueous sodium hydroxyde solution are added
  9. extractionthe aqueous mixture is extracted once with toluene
  10. washThe organic phase is washed once with water
  11. dry with materialdried over anhydrous sodium sulphate
  12. customthe solvents are evaporated off with a rotative evaporator until dryness
  13. filtrationfiltered
  14. additiona 4.38 N alcoholic hydrochloric acid solution (17.5 ml) is added to the isopropanol solution
  15. customto crystallize
  16. filtrationThe precipitate is filtered
  17. washwashed with isopropanol and diethyl ether
  18. customdried in vacuo

Sources & evidence

ORD record
ord-79e518cc705b4e239fb3601bcdd0c04d
Source dataset
uspto-grants-2002_01
Patent number
US06335331B1

Reaction notes

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