Morpholine → 4-Morpholinopiperidine

HRID 2216392Notes

Reaction equation

HRID 2216392 reaction equation
C(OC([N:6]1[CH2:11][CH2:10][C:9](=O)[CH2:8][CH2:7]1)=O)C.[NH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1>C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC=CC=1>[O:16]1[CH2:17][CH2:18][N:13]([CH:9]2[CH2:8][CH2:7][NH:6][CH2:11][CH2:10]2)[CH2:14][CH2:15]1

Participants

5

Reactant 2

HCID 8083MorpholineHCID 34767Ethyl 4-oxo-1-piperidinecarboxylate

Product 1

HCID 7957244-MorpholinopiperidineYield 67.6%

Reagents, catalysts & solvents 2

HCID 6101p-Toluenesulfonic acidCatalystHCID 1140TolueneSolvent

Procedure

1-Ethoxycarbonyl-4-piperidone (250 g), morpholine (152.0 g) and p-toluenesulfonic acid (5 g) were added to toluene (600 ml) and the mixture was heated under reflux for 15 hr with dehydration. Then, the solvent was evaporated and the obtained oily component was added to a suspension of ethanol (1L) containing sodium borohydride (58 g) under ice-cooling. The mixture was further stirred at room temperature for 10 hr. The reaction mixture was treated with diluted hydrochloric acid and the solvent was evaporated under reduced pressure. Thereto were added 2-propanol (2 L) and potassium hydroxide (365 g) and the mixture was heated under reflux at 80° C. for 15 hr. The solvent was evaporated under reduced pressure. The obtained oily component was purified by distillation to give the title compound (168 g).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 15 hr with dehydration
  3. customThen, the solvent was evaporated
  4. additionthe obtained oily component was added to a suspension of ethanol (1L)
  5. additioncontaining sodium borohydride (58 g) under ice-
  6. temperaturecooling
  7. additionThe reaction mixture was treated with diluted hydrochloric acid
  8. customthe solvent was evaporated under reduced pressure
  9. additionThereto were added 2-propanol (2 L) and potassium hydroxide (365 g)
  10. temperaturethe mixture was heated
  11. temperatureunder reflux at 80° C. for 15 hr
  12. customThe solvent was evaporated under reduced pressure
  13. distillationThe obtained oily component was purified by distillation

Sources & evidence

ORD record
ord-6c2f1d1de31e4045bb63c0ea15f12496
Source dataset
uspto-grants-2006_09
Patent number
US07112594B2

Reaction notes

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