Hydrochloric Acid → 4-Benzyl-6-(3,4-dichlorophenyl)-6-[2-[4-phenyl-4-(pyrrolidin-1-ylcarbonyl)piperid-1-yl]ethyl]morpholin-3-one hydrochloride monohydrate

HRID 1601912Notes

Reaction equation

HRID 1601912 reaction equation
[CH2:1]([N:8]1[CH2:13][C:12]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([Cl:28])[CH:22]=2)([CH2:14][CH2:15]OS(C)(=O)=O)[O:11][CH2:10][C:9]1=[O:29])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:30]1([C:36]2([C:42]([N:44]3[CH2:48][CH2:47][CH2:46][CH2:45]3)=[O:43])[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C([O-])([O-])=O.[K+].[K+].Cl>CN(C=O)C.C(Cl)Cl.CCOCC.O>[OH2:11].[ClH:27].[CH2:1]([N:8]1[CH2:13][C:12]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([Cl:28])[CH:22]=2)([CH2:14][CH2:15][N:39]2[CH2:40][CH2:41][C:36]([C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)([C:42]([N:44]3[CH2:48][CH2:47][CH2:46][CH2:45]3)=[O:43])[CH2:37][CH2:38]2)[O:11][CH2:10][C:9]1=[O:29])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 30194854-Phenyl-4-(pyrrolidin-1-ylcarbonyl)piperidineHCID 195913894-Benzyl-6-(3,4-dichlorophenyl)-6-[2-(methanesulfonyloxy)ethyl]morpholin-3-one

Product 1

HCID 212005114-Benzyl-6-(3,4-dichlorophenyl)-6-[2-[4-phenyl-4-(pyrrolidin-1-ylcarbonyl)piperid-1-yl]ethyl]morpholin-3-one hydrochloride monohydrateYield 58.2%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 0.98 g of the compound obtained in step B of EXAMPLE 14, 0.645 g of 4-phenyl-4-(pyrrolidin-1-ylcarbonyl)piperidine and 0.69 g of K2CO3 in 3 ml of DMF is heated at 80° C. for 2 hours. After cooling to RT, the reaction mixture is poured into water and extracted with an AcOEt/ether mixture, 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 H using a DCM/MeOH mixture (100/2; v/v) as the eluent. The product obtained is dissolved in the minimum amount of DCM and acidified to pH 1 by the addition of a saturated solution of gaseous HCl in ether and the precipitate formed is wrung to give 0.42 g of the expected product. M.p.=155-178° C.

Workup

  1. temperatureAfter cooling to RT
  2. extractionextracted with an AcOEt/ether mixture
  3. washthe organic phase is washed with water
  4. dry with materialdried over MgSO4
  5. customthe solvent is evaporated off under vacuum
  6. customThe residue is chromatographed on silica H
  7. customThe product obtained
  8. customthe precipitate formed

Sources & evidence

ORD record
ord-025adbd5efd642d3b1c164687ca2986a
Source dataset
uspto-grants-1999_11
Patent number
US05977359

Reaction notes

Loading…