Water → 1-Benzoyl-3-(3,4-dichlorophenyl)-3-[3-(4-piperidinopiperid-1-yl)propyl]-piperidine dihydrochloride hemihydrate

HRID 50059

Reaction equation

HRID 50059 reaction equation
[N:1]1([CH:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[ClH:13].[C:14]([N:22]1[CH2:27][CH2:26][CH2:25][C:24]([C:44]2[CH:49]=[CH:48][C:47]([Cl:50])=[C:46]([Cl:51])[CH:45]=2)([CH2:28][CH2:29][CH2:30][N:31]2[CH2:36][CH2:35][CH:34](C(N3CCCC3)=O)[CH2:33][CH2:32]2)[CH2:23]1)(=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C.C(#N)C.CCOC(C)=O>[OH2:21].[ClH:50].[ClH:13].[C:14]([N:22]1[CH2:27][CH2:26][CH2:25][C:24]([C:44]2[CH:49]=[CH:48][C:47]([Cl:50])=[C:46]([Cl:51])[CH:45]=2)([CH2:28][CH2:29][CH2:30][N:10]2[CH2:11][CH2:12][CH:7]([N:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)[CH2:8][CH2:9]2)[CH2:23]1)(=[O:21])[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1.[C:14]([N:22]1[CH2:27][CH2:26][CH2:25][C:24]([CH2:28][CH2:29][CH2:30][N:31]2[CH2:32][CH2:33][CH:34]([N:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)[CH2:35][CH2:36]2)([C:44]2[CH:49]=[CH:48][C:47]([Cl:50])=[C:46]([Cl:51])[CH:45]=2)[CH2:23]1)(=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[ClH:50].[ClH:50]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 786071,4'-BipiperidineHCID 227417141-Benzoyl-3-(3,4-dichlorophenyl)-3-[3-[4-(pyrrolidin-1-ylcarbonyl)piperid-1-yl]propyl]piperidine hydrochloride

Product 1

HCID 1317216521-Benzoyl-3-(3,4-dichlorophenyl)-3-[3-(4-piperidinopiperid-1-yl)propyl]-piperidine dihydrochloride hemihydrate

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21891449acetonitrile N,N-dimethylformamideSolvent

Conditions

Temperature
100 °C

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.).

Workup

  1. extractionextracted with AcOEt
  2. washthe organic phase is washed twice with water and with saturated NaCl solution
  3. dry with materialdried over MgSO4
  4. customthe solvent is evaporated off under vacuum
  5. customThe residue is chromatographed on silica H
  6. customThe product obtained
  7. customa stream of HCl gas is bubbled into the solution until the pH is 1, and ether
  8. additionis added until precipitation
  9. filtrationThis gives 0.53 g of the expected product after filtration
  10. customdrying

Sources & evidence

ORD record
ord-f5b4b110951240c1b5c5e985d48e12ea
Source dataset
uspto-grants-2004_03
Patent number
US06710042B2

Linked notes

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