Water → 4-(2H-1,3-Benzodioxol-5-yl)piperidin-4-ol

HRID 1670762Notes

Reaction equation

HRID 1670762 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]2[O:8][CH2:9][O:10][C:4]=2[CH:3]=1.CCCCCC.C([Li])CCC.C(OC([N:27]1[CH2:32][CH2:31][C:30](=[O:33])[CH2:29][CH2:28]1)=O)C.O>O1CCCC1>[O:8]1[C:5]2[CH:6]=[CH:7][C:2]([C:30]3([OH:33])[CH2:31][CH2:32][NH:27][CH2:28][CH2:29]3)=[CH:3][C:4]=2[O:10][CH2:9]1

Participants

6

Reactant 4

HCID 962WaterHCID 34767Ethyl 4-oxo-1-piperidinecarboxylateHCID 758311-Bromo-3,4-(methylenedioxy)benzeneHCID 178418244HCID 178418244, compound

Product 1

HCID 150347154-(2H-1,3-Benzodioxol-5-yl)piperidin-4-olYield 45.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

4-Bromo-1,2-(methylenedioxy)benzene (Tokyo Chemical Industry CO., LTD., 2.0 g) was dissolved in tetrahydrofuran (15 ml) and the mixture was cooled to −78° C. An n-butyllithium hexane solution (2.44 M, 5.7 ml) was added to the solution. The mixture was stirred at −78° C. for 1 hr, and 1-(ethoxycarbonyl)-4-piperidone (Aldrich Co., 1.7 g) was added. Then, the reaction temperature was raised to 0° C., and the mixture was further stirred for 1 hr. After completion of the reaction, water was added and the mixture was extracted three times with ethyl acetate. The organic layer was dried and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (elution solvent: hexane-ethyl acetate (5:1-2:1)). Then, the residue was dissolved in ethylene glycol (20 ml), a 50% aqueous potassium hydroxide solution was added, and the mixture was stirred with heating at 120° C. for 6 hr. After completion of the reaction, the mixture was extracted three times with chloroform. The organic layer was dried and the solvent was evaporated under reduced pressure to give 4-(1,3-benzodioxol-5-yl)piperidin-4-ol (1.0 g, yield 43%).

Workup

  1. temperatureThen, the reaction temperature was raised to 0° C.
  2. stirringthe mixture was further stirred for 1 hr
  3. additionwas added
  4. extractionthe mixture was extracted three times with ethyl acetate
  5. customThe organic layer was dried
  6. customthe solvent was evaporated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (elution solvent: hexane-ethyl acetate (5:1-2:1))
  8. dissolutionThen, the residue was dissolved in ethylene glycol (20 ml)
  9. additiona 50% aqueous potassium hydroxide solution was added
  10. stirringthe mixture was stirred
  11. temperaturewith heating at 120° C. for 6 hr
  12. customAfter completion of the reaction
  13. extractionthe mixture was extracted three times with chloroform
  14. customThe organic layer was dried
  15. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-f5fc5cbec53844e7b034826221f9ae0b
Source dataset
uspto-grants-2011_08
Patent number
US07994196B2

Reaction notes

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