p-Toluenesulfonic acid monohydrate → Methyl 3-(4-oxopiperidin-1-yl)benzoate

HRID 1051984Notes

Reaction equation

HRID 1051984 reaction equation
[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([N:10]2[CH2:19][CH2:18][C:13]3(OCC[O:14]3)[CH2:12][CH2:11]2)[CH:5]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>O.CC(C)=O>[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([N:10]2[CH2:19][CH2:18][C:13](=[O:14])[CH2:12][CH2:11]2)[CH:5]=1

Participants

5

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 60059302Methyl-3-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)benzoate

Product 1

HCID 60059322Methyl 3-(4-oxopiperidin-1-yl)benzoateYield 79.3%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

A mixture of methyl-3-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)-benzoate (1.80 g, 6.49 mmol) and p-toluenesulfonic acid monohydrate (123 mg, 0.649 mmol) in water (30 mL) and acetone (15 mL) was heated at reflux for 17 hours. The organic solvent was removed in vacuo and the aqueous mixture was extracted with dichloromethane. The organic extract was washed with saturated NaHCO3(aq.), dried (MgSO4), filtered and concentrated. Elution through a flash column (silica gel 60, 230-400 mesh, 3:2 hexanes:EtOAc) followed by concentration gave the title compound as a yellow oil (1.20 g, 79%).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 17 hours
  3. customThe organic solvent was removed in vacuo
  4. extractionthe aqueous mixture was extracted with dichloromethane
  5. extractionThe organic extract
  6. washwas washed with saturated NaHCO3(aq.)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. washElution through a flash column (silica gel 60, 230-400 mesh, 3:2 hexanes:EtOAc)
  11. concentrationfollowed by concentration

Sources & evidence

ORD record
ord-305e114f647749b1b006460427ae49b7
Source dataset
uspto-grants-2016_07
Patent number
US09388176B2

Reaction notes

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