4-Butyloxyaniline → N-(4-n-butoxyphenyl)-2-(1-benzyl-4-hydroxypiperidin-4-yl)acetamide

HRID 49961

Reaction equation

HRID 49961 reaction equation
[Li+].[CH2:2]([N:9]1[CH2:14][CH2:13][C:12]([CH2:16][C:17]([O-:19])=O)([OH:15])[CH2:11][CH2:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:20]([O:24][C:25]1[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][CH:26]=1)[CH2:21][CH2:22][CH3:23].P(Cl)(Cl)(Cl)=O.C(=O)(O)[O-].[Na+]>C(Cl)Cl.N1C=CC=CC=1>[CH2:20]([O:24][C:25]1[CH:26]=[CH:27][C:28]([NH:29][C:17](=[O:19])[CH2:16][C:12]2([OH:15])[CH2:11][CH2:10][N:9]([CH2:2][C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH2:14][CH2:13]2)=[CH:30][CH:31]=1)[CH2:21][CH2:22][CH3:23]

Participants

7

Reactant 4

HCID 203524-ButyloxyanilineHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 69894340(1-Benzyl-4-hydroxypiperidin-4-yl) acetic acid lithium salt

Product 1

HCID 17823865N-(4-n-butoxyphenyl)-2-(1-benzyl-4-hydroxypiperidin-4-yl)acetamideYield 24%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
7.5 °C

Procedure

To a solution of (1-benzyl-4-hydroxypiperidin-4-yl) acetic acid lithium salt (3.09 g) in methylene chloride (60 mL) were added 4-n-butoxyaniline (2.0 g) and pyridine (2.14 mL). Phosphorous oxychloride (1.19 mL) was added dropwise to the solution under cooling with an ice-sodium chloride, followed by stirring at 5 to 10° C. for 1 hour. The mixture was made alkaline with saturated aqueous sodium bicarbonate under cooling with an ice-water, and the solution was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried over anhydrous sodium sulfate, and then, the solvent was distilled off under reduced pressure. The residue was purified with silica gel column chromatography (elution solvent; methylene chloride:methanol=19:1 to 9:1) to obtain the titled compound (1.15 g).

Workup

  1. extractionthe solution was extracted with ethyl acetate
  2. washThe organic layer was washed with water and saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. distillationthe solvent was distilled off under reduced pressure
  5. customThe residue was purified with silica gel column chromatography (elution solvent; methylene chloride:methanol=19:1 to 9:1)

Sources & evidence

ORD record
ord-23334740640f45f081f14beef34c204b
Source dataset
uspto-grants-2004_03
Patent number
US06710060B2

Linked notes

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