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

HRID 1862565Notes

Reaction equation

HRID 1862565 reaction equation
C=O.[CH2:3]([NH2:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH3:11][CH:12](C)[C:13](=[O:15])C.Cl.C=O.[CH2:20](N)C1C=CC=CC=1.C(N([CH:34]([CH3:36])[CH3:35])CC)(C)C.[OH-].[K+]>C(O)C.O>[CH2:3]([N:10]1[CH2:11][CH2:12][C:13](=[O:15])[C:34]([CH3:35])([CH3:36])[CH2:20]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 712Formaldehyde2×HCID 7504BenzylamineHCID 112513-Methyl-2-butanoneHCID 14797Potassium HydroxideHCID 81531DiisopropylethylamineHCID 8659040590367-39-8

Product 1

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

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 962WaterSolvent

Conditions

Temperature
10 °C

Procedure

In a 1 liter 3-necked flask equipped with mechanical stirring, addition funnel and a calcium chloride drying tube is added a 37% weight solution of formaldehyde (168.5 mL, 2.25 mole) dissolved in 500 mL of absolute ethanol. The resulting solution is cooled in an ice-water bath to 10° C., and benzylamine (109 mL, 1 mole) is added dropwise over a one hour period. In a separate 3 liter 3-necked flask equipped with mechanical stirring, addition funnel and two condensers is added 3-methyl-2-butanone (113 mL, 1.06 mole) dissolved in 500 ml of absolute ethanol and concentrated hydrogen chloride (92 mL, 1.11 mole). The resulting solution is brought to reflux and the formaldehyde/benzylamine solution is added dropwise over a 2 hour period. This solution is refluxed overnight, and then cooled to ambient temperature. Diisopropylethylamine (142.2 g, 1.1 mole) and formaldehyde (22.46 mL, 0.3 mole) are added and the resulting solution is heated to reflux for six hours, and then cooled to ambient temperature. The solution is quenched with potassium hydroxide (61.6 g, 1.1 mole) in 200 mL of water, and then extracted with 500 mL ethyl acetate three times. The organics are concentrated under vacuum to give 225 g of red oil. The crude oil is dissolved in 1 liter of methylene chloride. This solution is carefully poured over 1 kg of silica gel on a sintered glass filter. The silica gel is washed with 4 L of methylene chloride. The methylene chloride is concentrated under vacuum to provide 142 g of a yellow oil which crystallizes in the freezer overnight. Yield=65.4%.

Workup

  1. customIn a 1 liter 3-necked flask equipped with mechanical stirring, addition funnel and a calcium chloride drying tube
  2. customIn a separate 3 liter 3-necked flask equipped with mechanical stirring, addition funnel and two condensers
  3. temperatureto reflux
  4. temperatureThis solution is refluxed overnight
  5. temperaturecooled to ambient temperature
  6. temperaturethe resulting solution is heated
  7. temperatureto reflux for six hours
  8. temperaturecooled to ambient temperature
  9. extractionextracted with 500 mL ethyl acetate three times
  10. concentrationThe organics are concentrated under vacuum

Sources & evidence

ORD record
ord-67dda25cc20c4ccbb35239327630ac40
Source dataset
uspto-grants-2003_03
Patent number
US06538136B1

Reaction notes

Loading…