Hydrochloric Acid → 6-[2-[4-(Acetyl-N-methylamino)-4-phenylpiperid-1-yl]ethyl]-4-benzyl-6-(3,4-dichlorophenyl)morpholin-3-one hydrochloride monohydrate

HRID 1601913Notes

Reaction equation

HRID 1601913 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.C1(C)C=CC(S(O)(=O)=O)=CC=1.[C:41]([N:44]([C:46]1([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]1)[CH3:45])(=[O:43])[CH3:42].C([O-])([O-])=O.[K+].[K+].Cl>CN(C=O)C.C(Cl)Cl.CCOCC.O>[OH2:11].[ClH:27].[C:41]([N:44]([C:46]1([C:52]2[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=2)[CH2:47][CH2:48][N:49]([CH2:15][CH2:14][C:12]2([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([Cl:28])[CH:22]=3)[CH2:13][N:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[C:9](=[O:29])[CH2:10][O:11]2)[CH2:50][CH2:51]1)[CH3:45])(=[O:43])[CH3:42]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 195913894-Benzyl-6-(3,4-dichlorophenyl)-6-[2-(methanesulfonyloxy)ethyl]morpholin-3-oneHCID 227417314-(acetyl-N-methylamino)-4-phenylpiperidine p-toluenesulfonate

Product 1

HCID 212005966-[2-[4-(Acetyl-N-methylamino)-4-phenylpiperid-1-yl]ethyl]-4-benzyl-6-(3,4-dichlorophenyl)morpholin-3-one hydrochloride monohydrateYield 79.6%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 1.1 g of the compound obtained in step B of EXAMPLE 14, 1.85 g of 4-(acetyl-N-methylamino)-4-phenylpiperidine p-toluenesulfonate and 1.3 g of K2CO3 in 3 ml of DMF is heated at 80-100° C. for 2 hours. After cooling to RT, the reaction mixture is poured into water and extracted with ether, 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 (from 100/1; v/v to 100/4; v/v) as the eluent. The product obtained is dissolved in DCM, a saturated solution of hydrochloric acid in ether is added until the pH is 1, and the precipitate formed is wrung to give 0.62 g of the expected product. M.p.=148-150° C.

Workup

  1. temperatureAfter cooling to RT
  2. extractionextracted with ether
  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-e8d61d874acd42c8918a4473153d5b80
Source dataset
uspto-grants-1999_11
Patent number
US05977359

Reaction notes

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