Reaction #78337

Reaction equation

water

4-piperidinopiperidine

compound

1-Benzoyl-3-(3,4-dichlorophenyl)-3-[3-[4-(pyrrolidin-1-ylcarbonyl)piperid-1-yl]propyl]piperidine Hydrochloride

K2CO3

→

1-Benzoyl-3-(3,4-dichlorophenyl)-3-[3-(4-piperidinopiperid-1-yl)propyl]-piperidine Dihydrochloride Hemihydrate

Solvents

AcOEt

DMF acetonitrile

Conditions

Workup

1. 1
   Extractionextracted with AcOEt
2. 2
   Washthe organic phase is washed twice with water and with saturated NaCl solution
3. 3
   Dryingdried over MgSO4
4. 4
   Otherthe solvent is evaporated off under vacuum
5. 5
   OtherThe residue is chromatographed on silica H
6. 6
   OtherThe product obtained
7. 7
   Othera stream of HCl gas is bubbled into the solution until the pH is 1, and ether
8. 8
   workup.ADDITIONis added until precipitation
9. 9
   FiltrationThis gives 0.53 g of the expected product after filtration
10. 10
    Otherdrying

Procedure

A mixture of 0.55 g of 4-piperidinopiperidine, 1.3 g of the compound obtained in step B of EXAMPLE 1 and 1.14 g of K2CO3 in 10 ml of a DMF/acetonitrile mixture (50/50; v/v) is heated at 100° C. for 3 hours. The reaction mixture is poured into water and extracted with AcOEt, the organic phase is washed twice with water and with saturated NaCl solution and dried over MgSO4 and the solvent is evaporated off under vacuum. The residue is chromatographed on silica H using DCM and then a DCM/MeOH mixture (98/2; v/v) as the eluent. The product obtained is dissolved in AcOEt, a stream of HCl gas is bubbled into the solution until the pH is 1, and ether is added until precipitation occurs. This gives 0.53 g of the expected product after filtration and drying, m.p.=265° C. (dec.).

Source