Hydrochloric Acid → 1-Benzoyl-3-(3,4-dichlorophenyl)-3-[3-[4-(2-hydroxyethoxy)-4-phenylpiperid-1-yl]propyl]piperidine hydrochloride monohydrate

HRID 1597092Notes

Reaction equation

HRID 1597092 reaction equation
Cl.[OH:2][CH2:3][CH2:4][O:5][C:6]1([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]1.[C:18]([N:26]1[CH2:31][CH2:30][CH2:29][C:28]([C:40]2[CH:45]=[CH:44][C:43]([Cl:46])=[C:42]([Cl:47])[CH:41]=2)([CH2:32][CH2:33][CH2:34]OS(C)(=O)=O)[CH2:27]1)(=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C([O-])([O-])=O.[K+].[K+].Cl>CN(C=O)C.C(Cl)Cl.O>[OH2:2].[ClH:46].[C:18]([N:26]1[CH2:31][CH2:30][CH2:29][C:28]([C:40]2[CH:45]=[CH:44][C:43]([Cl:46])=[C:42]([Cl:47])[CH:41]=2)([CH2:32][CH2:33][CH2:34][N:9]2[CH2:8][CH2:7][C:6]([O:5][CH2:4][CH2:3][OH:2])([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH2:11][CH2:10]2)[CH2:27]1)(=[O:25])[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 118127101-Benzoyl-3-(3,4-dichlorophenyl)-3-[3-(methanesulfonyloxy)propyl]piperidineHCID 227417534-(2-Hydroxyethoxy)-4-phenylpiperidine hydrochloride

Product 1

HCID 227418231-Benzoyl-3-(3,4-dichlorophenyl)-3-[3-[4-(2-hydroxyethoxy)-4-phenylpiperid-1-yl]propyl]piperidine hydrochloride monohydrateYield 102.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 1 g of 4-(2-hydroxyethoxy)-4-phenylpiperidine hydrochloride, 1.7 g of the compound obtained in step B of EXAMPLE 1 and 0.65 g of K2CO3 in 15 ml of DMF is heated at 60° C. for 2 hours and the reaction mixture is then stirred overnight at RT. It is poured into water and extracted with DCM, the organic phase is washed with water and dried over Na2SO4 and the solvent is evaporated off under vacuum. The residue is chromatographed on silica H using DCM and then a DCM/MeOH mixture (96/4; v/v) as the eluent. The product obtained is dissolved in DCM and acidified by the addition of ethereal hydrogen chloride and the precipitate formed is filtered off to give 1.2 g of the expected product, m.p.=120-123° C.

Workup

  1. extractionextracted with DCM
  2. washthe organic phase is washed with water
  3. dry with materialdried over Na2SO4
  4. customthe solvent is evaporated off under vacuum
  5. customThe residue is chromatographed on silica H
  6. customThe product obtained
  7. customthe precipitate formed
  8. filtrationis filtered off

Sources & evidence

ORD record
ord-9576fdd85e3145da953a20af9876da17
Source dataset
uspto-grants-2001_09
Patent number
US06291672B1

Reaction notes

Loading…