Azobisisobutyronitrile → 3-(Piperidin-1-ylmethyl)benzoic acid

HRID 1416212Notes

Reaction equation

HRID 1416212 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7]C)=[O:6].BrN1C(=O)CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N.[NH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1.C(=O)([O-])[O-].[K+].[K+].[OH-].[K+]>C(Cl)(Cl)(Cl)Cl.CN(C)C=O.C(Cl)(Cl)Cl.C(O)(=O)C.C(O)C.O>[N:32]1([CH2:1][C:2]2[CH:3]=[C:4]([CH:9]=[CH:10][CH:11]=2)[C:5]([OH:7])=[O:6])[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1

Participants

13

Reactant 6

HCID 6547AzobisisobutyronitrileHCID 7435Benzoic acid, 3-methyl-, methyl esterHCID 8082PiperidineHCID 11430Potassium CarbonateHCID 14797Potassium HydroxideHCID 67184N-bromobutanimide

Product 1

HCID 4091993-(Piperidin-1-ylmethyl)benzoic acidYield 37.1%

Reagents, catalysts & solvents 6

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 5943Carbon TetrachlorideSolventHCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

Methyl 3-methylbenzoate (45.0 g), N-bromosuccinimide (53.4 g) and a catalitic amount of azobisisobutyronitrile were refluxed in carbon tetrachloride (500 ml) with stirring for 24 hours. The reaction mixture was filtered and the filtrate was concentrated under a vacuum. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=20:1), thereby yielding an oil. The oil was dissolved in dimethylformamide (1.5 l) and the mixture, with piperidine (63.2 g) and potassium carbonate (205 g) added thereto, was stirred all day and night at room temperature. The reaction mixture, with water added thereto, was extracted with ethyl acetate. The extract was dried over sodium sulfate anhydride, and then concentrated under a vacuum. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1), thereby yielding an oil. Potassium hydroxide (78.0 g), water (325 ml), and ethanol (325 ml) were added to the oil and the mixture was refluxed with stirring for 2 hours. After being neutralized with acetic acid, the reaction mixture, with chloroform added thereto, was filtered. The filtrate was concentrated under a vacuum. The resulting solid was washed with ethanol, thereby yielding 24.4 g of the aimed compound. The resulting solid was washed with ethanol, thereby yielding 24.4 g of the aimed compound.

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationthe filtrate was concentrated under a vacuum
  3. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=20:1)
  4. customyielding an oil
  5. stirringwas stirred all day and night at room temperature
  6. extractionwas extracted with ethyl acetate
  7. dry with materialThe extract was dried over sodium sulfate anhydride
  8. concentrationconcentrated under a vacuum
  9. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1)
  10. customyielding an oil
  11. temperaturethe mixture was refluxed
  12. stirringwith stirring for 2 hours
  13. filtrationwas filtered
  14. concentrationThe filtrate was concentrated under a vacuum
  15. washThe resulting solid was washed with ethanol

Sources & evidence

ORD record
ord-a3b614af70964ce58c9be99d99ef451b
Source dataset
uspto-grants-1999_06
Patent number
US05912258

Reaction notes

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