Acetaldehyde → trans-N-Benzyl-2,6-dimethylpiperidin-4-one

HRID 15736Notes

Reaction equation

HRID 15736 reaction equation
[CH3:1][C:2]([CH3:4])=O.[CH:5]([OH:7])=O.C(O)=O.[CH:11](=O)[CH3:12].[CH2:14]([NH2:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.Cl.[C:23](=O)(O)[O-].[Na+]>O>[CH2:14]([N:21]1[C@@H:2]([CH3:4])[CH2:1][C:5](=[O:7])[CH2:23][C@@H:11]1[CH3:12])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

7

Reactant 5

HCID 177AcetaldehydeHCID 313Hydrochloric AcidHCID 7504BenzylamineHCID 516892Sodium BicarbonateHCID 53400708Acetone dicarboxylic acid

Product 1

HCID 68495982trans-N-Benzyl-2,6-dimethylpiperidin-4-one

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

The 1 L 3-necked roundbottom flask, equipped with mechanical stirrer, reflux condenser, thermometer and addition funnel was charged with the solution of acetone dicarboxylic acid (40 g, 0.28 mol) in water (100 ml). The stirred solution was treated with acetaldehyde (25.3 g. 0.55 mol) at ambient temp. for 10 min., then benzylamine (30 ml, 0.28 mol) was added in small portions over 15 min. Vigorous gas evolution was observed and was moderated by use of a cooling bath (ice-water). The resulting yellow solution was stirred at ambient temperature for 78 hr. The stirred reaction mixture was acidified with aq. 1 N HCl to pH2, stirred for 1 hr then neutralized with aq. sodium bicarbonate to pH7 and extracted with CH2Cl2 (3×250 ml). Combined extracts were washed with brine and dried with anhydrous Na2SO4. The solution was filtered and evaporated to give brown liquid, 57 g. The isomeric piperidinones were separated by flash chromatography, eluting with CH2Cl2-EtOAc (9:1). The yield of the first-eluting compound, identified as the cis-isomer was 20 g. The yield of the second-eluting compound, identified as the trans-isomer was 25 g. A small amount of unresolved material was also collected (ca. 4.7 g).

Workup

  1. customThe 1 L 3-necked roundbottom flask, equipped with mechanical stirrer
  2. temperaturereflux condenser
  3. additionthermometer and addition funnel
  4. customwas moderated by use of a cooling bath
  5. customThe stirred reaction mixture
  6. stirringstirred for 1 hr
  7. extractionextracted with CH2Cl2 (3×250 ml)
  8. washCombined extracts were washed with brine
  9. dry with materialdried with anhydrous Na2SO4
  10. filtrationThe solution was filtered
  11. customevaporated
  12. customto give brown liquid, 57 g
  13. customThe isomeric piperidinones were separated by flash chromatography
  14. washeluting with CH2Cl2-EtOAc (9:1)
  15. customA small amount of unresolved material was also collected (ca. 4.7 g)

Sources & evidence

ORD record
ord-77b0c7f47d114deeadba7b49f35949ca
Source dataset
uspto-grants-2010_06
Patent number
US07732609B2

Reaction notes

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