Hydrochloric Acid → 1-Benzoyl-3-[3-[4-benzyl-4-(pyrrolidin-1-ylcarbonyl)piperid-1-yl]propyl]-3-(3,4-dichlorophenyl)piperidine hydrochloride hemihydrate

HRID 50067Notes

Reaction equation

HRID 50067 reaction equation
[C:1]1([CH3:11])[CH:6]=[CH:5][C:4](S(O)(=O)=[O:8])=[CH:3][CH:2]=1.[CH2:12]([C:19]1([C:25]([N:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)=[O:26])[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[ClH:32].[C:33]([N:41]1[CH2:46][CH2:45][CH2:44][C:43]([C:63]2[CH:68]=[CH:67][C:66]([Cl:69])=[C:65]([Cl:70])[CH:64]=2)([CH2:47][CH2:48][CH2:49][N:50]2[CH2:55][CH2:54][CH:53]([C:56]([N:58]3[CH2:62][CH2:61][CH2:60][CH2:59]3)=[O:57])[CH2:52][CH2:51]2)[CH2:42]1)(=[O:40])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C([O-])([O-])=O.[K+].[K+].Cl>CN(C=O)C.O>[OH2:8].[ClH:69].[C:33]([N:41]1[CH2:46][CH2:45][CH2:44][C:43]([CH2:47][CH2:48][CH2:49][N:22]2[CH2:23][CH2:24][C:19]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)([C:25]([N:27]3[CH2:31][CH2:30][CH2:29][CH2:28]3)=[O:26])[CH2:20][CH2:21]2)([C:63]2[CH:68]=[CH:67][C:66]([Cl:69])=[C:65]([Cl:70])[CH:64]=2)[CH2:42]1)(=[O:40])[C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1.[C:33]([N:41]1[CH2:46][CH2:45][CH2:44][C:43]([C:63]2[CH:68]=[CH:67][C:66]([Cl:69])=[C:65]([Cl:70])[CH:64]=2)([CH2:47][CH2:48][CH2:49][N:50]2[CH2:51][CH2:52][C:53]([C:56]([N:58]3[CH2:59][CH2:60][CH2:61][CH2:62]3)=[O:57])([CH2:11][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:54][CH2:55]2)[CH2:42]1)(=[O:40])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.[ClH:32]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 227417124-Benzyl-4-(pyrrolidin-1-ylcarbonyl)piperidine p-toluenesulfonateHCID 227417141-Benzoyl-3-(3,4-dichlorophenyl)-3-[3-[4-(pyrrolidin-1-ylcarbonyl)piperid-1-yl]propyl]piperidine hydrochloride

Product 1

HCID 1317216551-Benzoyl-3-[3-[4-benzyl-4-(pyrrolidin-1-ylcarbonyl)piperid-1-yl]propyl]-3-(3,4-dichlorophenyl)piperidine hydrochloride hemihydrate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-benzyl-4-(pyrrolidin-1-ylcarbonyl)piperidine p-toluene-sulfonate, 0.65 g of the compound obtained in step B of EXAMPLE 1 and 0.7 g of K2CO3 in 6 ml of DMF is heated at 80° C. for 3 hours. The reaction mixture is poured into iced water and the precipitate formed is filtered off and washed with water. The precipitate is dissolved in AcOEt, the organic phase is 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 (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 0.56 g of the expected product.

Workup

  1. customthe precipitate formed
  2. filtrationis filtered off
  3. washwashed with water
  4. dissolutionThe precipitate is dissolved in AcOEt
  5. dry with materialthe organic phase is dried over MgSO4
  6. customthe solvent is evaporated off under vacuum
  7. customThe residue is chromatographed on silica H
  8. customThe product obtained
  9. customthe precipitate formed
  10. filtrationis filtered off

Sources & evidence

ORD record
ord-960e5a400a17473e86c5082ea882ad5d
Source dataset
uspto-grants-2004_03
Patent number
US06710042B2

Reaction notes

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