1-(1-Benzylpiperidin-4-yl)-2-(2-chlorophenyl)ethanone → 4-(2-Chlorophenylacetyl)piperidine hydrochloride

HRID 606212Notes

Reaction equation

HRID 606212 reaction equation
C([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:23])[CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[Cl:22])[CH2:10][CH2:9]1)C1C=CC=CC=1>ClCCCl.ClC(OC(Cl)C)=O>[ClH:22].[Cl:22][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[CH2:15][C:14]([CH:11]1[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1)=[O:23]

Participants

4

Reactant 1

HCID 222484151-(1-Benzylpiperidin-4-yl)-2-(2-chlorophenyl)ethanone

Product 1

HCID 222485334-(2-Chlorophenylacetyl)piperidine hydrochlorideYield 162.3%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 5213051-Chloroethyl chloroformateSolvent

Procedure

After dissolving 252 mg of 1-(1-benzylpiperidin-4-yl)-2-(2-chlorophenyl)ethanone in 3 ml of 1,2-dichloroethane, 0.1 ml of 1-chloroethyl chloroformate was added while stirring on ice, and the mixture was heated to reflux for 1 hour. The reaction solution was concentrated under reduced pressure, 3 ml of methanol was added to the residue, and heating to reflux was continued for 30 minutes. The reaction solution was concentrated under reduced pressure, ethyl acetate was added to the residue and the precipitate was filtered out to obtain 171 mg of 4-(2-chlorophenylacetyl)piperidine hydrochloride. After then suspending 98 mg of the 4-(2-chlorophenylacetyl)piperidine hydrochloride in 3 ml of dichloromethane, 77 mg of 3-tert-butoxypyrazine-2-carboxaldehyde and 114 mg of sodium triacetoxyborohydride were added while stirring on ice, and the stirring was continued overnight at room temperature. A 1N sodium hydroxide solution was added to the reaction mixture to render it alkaline, and then extraction was performed with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate) to obtain the title compound (112 mg, 78% yield).

Workup

  1. additionwas added
  2. temperaturethe mixture was heated
  3. temperatureto reflux for 1 hour
  4. concentrationThe reaction solution was concentrated under reduced pressure, 3 ml of methanol
  5. additionwas added to the residue
  6. temperatureheating
  7. temperatureto reflux
  8. concentrationThe reaction solution was concentrated under reduced pressure, ethyl acetate
  9. additionwas added to the residue
  10. filtrationthe precipitate was filtered out

Sources & evidence

ORD record
ord-3e38b6f925ff4b0e8c0efa47b31716d7
Source dataset
uspto-grants-2011_03
Patent number
US07915274B2

Reaction notes

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