Acetonitrile → Methyl 4-({1-[2-(4-cyanophenyl)ethyl]-4-hydroxypiperidin-4-ylmethyl}amino)benzoate

HRID 967782Notes

Reaction equation

HRID 967782 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][N:11]2[CH2:18][CH2:17][C:14]3([CH2:16][O:15]3)[CH2:13][CH2:12]2)=[CH:5][CH:4]=1)#[N:2].[NH2:19][C:20]1[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][CH:21]=1.Cl([O-])(=O)(=O)=O.[Li+].C(#N)C>[Cl-].[Na+].O>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][N:11]2[CH2:18][CH2:17][C:14]([CH2:16][NH:19][C:20]3[CH:21]=[CH:22][C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:28][CH:29]=3)([OH:15])[CH2:13][CH2:12]2)=[CH:5][CH:4]=1)#[N:2]

Participants

6

Reactant 4

HCID 6342AcetonitrileHCID 12082Methyl 4-aminobenzoateHCID 23665649Lithium perchlorateHCID 858197211-[2-(4-Cyanophenyl)ethyl]piperidin-4-spiro-2'-oxirane

Product 1

HCID 22930224Methyl 4-({1-[2-(4-cyanophenyl)ethyl]-4-hydroxypiperidin-4-ylmethyl}amino)benzoateYield 36.6%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Procedure

A mixture of the compound (242 mg) obtained in Step 3 of Example 1, methyl 4-aminobenzoate (756 mg), anhydrous lithium perchlorate (106 mg) and anhydrous acetonitrile (1 mL) was heated under reflux for two hours under nitrogen atmosphere. To the mixture was added brine (5 mL) and the residue was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solid residue obtained by removal of the solvent was washed two times by suspending in tert-butyl methyl ether to obtain the titled compound (144 mg) as powder.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for two hours under nitrogen atmosphere
  3. extractionthe residue was extracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solid residue obtained by removal of the solvent
  7. washwas washed two times

Sources & evidence

ORD record
ord-c2fbf09071d7456495bcee6373d29275
Source dataset
uspto-grants-2005_10
Patent number
US06956046B2

Reaction notes

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