Reaction #78339

Reaction equation

compound

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

K2CO3

hydrogen chloride

4-(2-aminothiazol-4-yl)-4-phenylpiperidine

→

expected product

Yield 104.5%

3-[3-[4-(2-Aminothiazol-4-yl)-4-phenylpiperid-1-yl]propyl]-1-benzoyl-3-(3,4-dichlorophenyl)piperidine Dihydrochloride Monohydrate

Yield 104.5%

Solvents

DMF acetonitrile

Conditions

Workup

1. 1
   Temperatureis refluxed for 2 hours
2. 2
   ConcentrationThe reaction mixture is concentrated under vacuum
3. 3
   Extractionextracted with AcOEt
4. 4
   Washthe organic phase is washed with water
5. 5
   Dryingdried over MgSO4
6. 6
   Otherthe solvent is evaporated off under vacuum
7. 7
   OtherThe residue is chromatographed on silica using a gradient of a DCM/MeOH mixture (98/2; v/v to 95/5; v/v) as the eluent
8. 8
   OtherThe product obtained
9. 9
   Otherthe precipitate formed
10. 10
    Filtrationis filtered off

Procedure

A mixture of 1.04 g of 4-(2-aminothiazol-4-yl)-4-phenylpiperidine (compound of PREPARATION 1.4 in the form of the free base), 1.88 g of the compound obtained in step B of EXAMPLE 1 and 1.1 g of K2CO3 in 20 ml of a DMF/acetonitrile mixture (50/50; v/v) is refluxed for 2 hours. The reaction mixture is concentrated under vacuum, the residue is taken up with water and extracted with AcOEt, the organic phase is washed with water and dried over MgSO4 and the solvent is evaporated off under vacuum. The residue is chromatographed on silica using a gradient of a DCM/MeOH mixture (98/2; v/v to 95/5; v/v) as the eluent. The product obtained is taken up with ethereal hydrogen chloride and the precipitate formed is filtered off to give 1.2 g of the expected product after crystallization from AcOEt, m.p.=162-164° C.

Source