Water → 1-Benzyl-3-(3,4-dichlorophenyl)-4-piperidinone

HRID 1260911Notes

Reaction equation

HRID 1260911 reaction equation
[H-].[Na+].C(OC(=O)[CH2:7][CH2:8][N:9]([CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH2:10][CH:11]([C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=1)[C:12](OCC)=[O:13])C.O>C1(C)C=CC=CC=1.C(O)C>[CH2:25]([N:9]1[CH2:8][CH2:7][C:12](=[O:13])[CH:11]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=2)[CH2:10]1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

6

Reactant 3

HCID 962WaterHCID 24758Sodium hydrideHCID 68870481N-benzyl-N-[2-(3,4-dichlorophenyl)-3-ethoxy-3-oxopropyl]-beta-alanine ethyl ester

Product 1

HCID 180011661-Benzyl-3-(3,4-dichlorophenyl)-4-piperidinoneYield 73%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of sodium hydride (60% in oil, 4.85 g) in toluene (109 mL) was added a solution of the compound (34.6 g) obtained in step 3 in ethanol (25.1 mL), and the mixture was stirred at 75° C. for 2 hr. The reaction mixture was poured into water, and the resultant product was extracted with ethyl acetate. The organic layer was washed with brine and dried, and the solvent was evaporated under reduced pressure. A solution of the obtained residue (30.3 g) in concentrated hydrochloric acid (100 mL) and acetic acid (34 mL) was stirred at 140° C. for 5 hr. The reaction mixture was concentrated under reduced pressure, and the obtained residue was made basic with aqueous sodium hydroxide solution. The resultant product was extracted with ethyl acetate, and the organic layer was washed with brine and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 10→50% ethyl acetate/hexane) to give 1-benzyl-3-(3,4-dichlorophenyl)-4-piperidinone (18.2 g, 73%) as a colorless oil.

Workup

  1. extractionthe resultant product was extracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. customdried
  4. customthe solvent was evaporated under reduced pressure
  5. stirringA solution of the obtained residue (30.3 g) in concentrated hydrochloric acid (100 mL) and acetic acid (34 mL) was stirred at 140° C. for 5 hr
  6. concentrationThe reaction mixture was concentrated under reduced pressure
  7. extractionThe resultant product was extracted with ethyl acetate
  8. washthe organic layer was washed with brine
  9. customdried
  10. customthe solvent was evaporated under reduced pressure
  11. customThe obtained residue was purified by silica gel column chromatography (solvent gradient; 10→50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-17326d462b0e4e69bb02476fb3caef0b
Source dataset
uspto-grants-2013_06
Patent number
US08470816B2

Reaction notes

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