Hydrochloric Acid → 1-Benzyl-3,3-dimethylpiperidin-4-one

HRID 1815823Notes

Reaction equation

HRID 1815823 reaction equation
C(N)[C:2]1[CH:7]=[CH:6]C=[CH:4][CH:3]=1.[CH2:9]=O.[CH3:11][CH:12]([C:14](=[O:16])[CH3:15])[CH3:13].Cl.C([N:20]([CH2:23][CH3:24])[CH2:21]C)C.[OH-].[K+]>C(O)C>[CH2:23]([N:20]1[CH2:21][CH2:15][C:14](=[O:16])[C:12]([CH3:9])([CH3:13])[CH2:11]1)[C:24]1[CH:6]=[CH:7][CH:2]=[CH:3][CH:4]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 712Formaldehyde2×HCID 7504BenzylamineHCID 8471TriethylamineHCID 112513-Methyl-2-butanoneHCID 14797Potassium Hydroxide

Product 1

HCID 97944131-Benzyl-3,3-dimethylpiperidin-4-one

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
5 °C

Procedure

Benzylamine (214 g, 2 mol) is combined with formaldehyde (37% in water, 375 g, 4.5 mol) in ethanol (1 L) with occasional cooling. This biphasic mixture is added over a period of 90 minutes to a refluxing solution of 2-methyl-3-butanone (182 g, 2.11 mol) in anhydrous ethanol (1 L) and hydrochloric acid (209 g of 37% solution, 2.1 mol). The brownish solution is heated at reflux for an additional 18 hours. Then triethylamine (310 mL, 223.8 g, 2.21 mol) and formaldehyde (50 g, 36%, 0.6 mol) are added sequentially and the reaction mixture is heated at reflux for 24 hours. The reaction mixture is then cooled to 5° C. and treated with potassium hydroxide (117.6 g, 2.1 mol, dissolved in 200 mL of water). The reaction mixture is then extracted with heptane (2×500 mL) and methyl tert-butyl ether (2×500 mL). The organic extracts is then combined, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to provide the title compound, (339.36 g after 18% by volume of the above combined organic extracts was removed prior to concentration). This material was purified by chromatography on silica gel (methylene chloride/ethanol, 100:1) to provide purified title compound.

Workup

  1. temperatureThe brownish solution is heated
  2. temperatureat reflux for an additional 18 hours
  3. temperaturethe reaction mixture is heated
  4. temperatureat reflux for 24 hours
  5. extractionThe reaction mixture is then extracted with heptane (2×500 mL) and methyl tert-butyl ether (2×500 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-2339834047334f8aab15058e072c5f91
Source dataset
uspto-grants-2005_04
Patent number
US06881733B1

Reaction notes

Loading…