Triethylamine → trans-2,2-Dimethyl-propionic acid 1-benzyl-3-methyl-piperidin-4-yl ester

HRID 2267687Notes

Reaction equation

HRID 2267687 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH:10]([CH3:15])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:23][C:24]([CH3:29])([CH3:28])[C:25](Cl)=[O:26]>C1COCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][C@@H:11]([O:14][C:25](=[O:26])[C:24]([CH3:29])([CH3:28])[CH3:23])[C@H:10]([CH3:15])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 136114921-Benzyl-3-methylpiperidin-4-ol

Product 1

HCID 131728602trans-2,2-Dimethyl-propionic acid 1-benzyl-3-methyl-piperidin-4-yl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cis/trans mixture of 1-benzyl-3-methyl-piperidin-4-ol (50 g, 243 mmol, prepared as described in Can. J. Chem. (1972) 50, 803) in THF is added triethylamine (51 ml, 365 mmol) followed by 2,2-dimethyl-propionyl chloride (45 ml, 365 mmol). The reaction is exothermic and a precipitate is formed. The mixture is heated under reflux for 18 hours, cooled, filtered and washed with ether. The organic layers are washed with 1N—NaOH and brine, dried and evaporated. The crude is purified by chromatography on silicagel using hexane and EtOAc (5%) to give pure trans-isomer as a colourless oil.

Workup

  1. customa precipitate is formed
  2. temperatureThe mixture is heated
  3. temperatureunder reflux for 18 hours
  4. temperaturecooled
  5. filtrationfiltered
  6. washwashed with ether
  7. washThe organic layers are washed with 1N—NaOH and brine
  8. customdried
  9. customevaporated
  10. customThe crude is purified by chromatography on silicagel
  11. customto give pure trans-isomer as a colourless oil

Sources & evidence

ORD record
ord-62e4c582e0314b2c9f439ffa0fb1d51d
Source dataset
uspto-grants-2010_12
Patent number
US07858781B2

Reaction notes

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