Potassium Hydroxide → Cis-2-[2-benzyloxy-4-(1,1-dimethylheptyl)phenyl]-4-piperidinol

HRID 371152Notes

Reaction equation

HRID 371152 reaction equation
C(OC([N:6]1[CH2:11][CH2:10][C@H:9]([OH:12])[CH2:8][C@@H:7]1[C:13]1[CH:18]=[CH:17][C:16]([C:19]([CH3:27])([CH3:26])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])=[CH:15][C:14]=1[O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=O)C.[OH-].[K+]>C(O)C.C(O)CO.O>[CH2:29]([O:28][C:14]1[CH:15]=[C:16]([C:19]([CH3:26])([CH3:27])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[CH:17]=[CH:18][C:13]=1[C@H:7]1[CH2:8][C@@H:9]([OH:12])[CH2:10][CH2:11][NH:6]1)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

Participants

6

Reactant 2

HCID 14797Potassium HydroxideHCID 70413237N-Ethoxycarbonyl-cis-2-[2-benzyloxy-4-(1,1-dimethylheptyl)phenyl]-4-piperidinol

Product 1

HCID 70413103Cis-2-[2-benzyloxy-4-(1,1-dimethylheptyl)phenyl]-4-piperidinolYield 83%

Reagents, catalysts & solvents 3

HCID 174Ethylene GlycolSolventHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
185 °C

Procedure

To a solution of 4.62 g (9.59 mmole) of N-ethoxycarbonyl-cis-2-[2-benzyloxy-4-(1,1-dimethylheptyl)phenyl]-4-piperidinol in 5 ml ethanol is added a solution of 4.2 g (75 mmole) of potassium hydroxide in 25 ml ethylene glycol and 4.2 ml water. The resultant mixture is evaporated at reduced pressure to remove ethanol and is then heated to reflux (bath 185° C.). After 24 hours material boiling at 80°-100° C. is removed by distillation, 6 ml ethylene glycol is added and the reaction continued at reflux for 17 hours. After cooling, the mixture is added to 500 ml dichloromethane and 80 ml water. The organic extract is washed with 80 ml saturated sodium chloride, dried over magnesium sulfate and evaporated in vacuo. The resulting crude oil is purified via column chromatography on 300 g of silica gel eluting in 20 ml fractions with 2.5% triethylamine, 2.5% methanol, 95% ethyl ether (fractions 1-109) and 5% triethylamine, 5% methanol, 90% ethyl ether (fractions 110-200). Fractions 138-190 gave 3.13 g (83%) of the title compound.

Workup

  1. customThe resultant mixture is evaporated at reduced pressure
  2. customto remove ethanol
  3. temperatureis then heated
  4. customAfter 24 hours material boiling at 80°-100° C. is removed by distillation, 6 ml ethylene glycol
  5. additionis added
  6. temperatureat reflux for 17 hours
  7. temperatureAfter cooling
  8. additionthe mixture is added to 500 ml dichloromethane and 80 ml water
  9. extractionThe organic extract
  10. washis washed with 80 ml saturated sodium chloride
  11. dry with materialdried over magnesium sulfate
  12. customevaporated in vacuo
  13. customThe resulting crude oil is purified via column chromatography on 300 g of silica gel eluting in 20 ml fractions with 2.5% triethylamine, 2.5% methanol, 95% ethyl ether (fractions 1-109) and 5% triethylamine, 5% methanol, 90% ethyl ether (fractions 110-200)

Sources & evidence

ORD record
ord-40c76cfe81084bb48d656182b2370936
Source dataset
uspto-grants-1985_07
Patent number
US04529732

Reaction notes

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