Benzylamine → 1-Benzyl-2-methylpiperidin-4-one

HRID 2179393Notes

Reaction equation

HRID 2179393 reaction equation
[CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])(O)=O.[Na+].[CH2:14]=[CH:15][C:16](=[O:20])/[CH:17]=[CH:18]/[CH3:19]>C(#N)C>[CH2:1]([N:8]1[CH2:14][CH2:15][C:16](=[O:20])[CH2:17][CH:18]1[CH3:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 7504BenzylamineHCID 516892Sodium BicarbonateHCID 12596784(E)-hexa-1,4-dien-3-one

Product 1

HCID 110957071-Benzyl-2-methylpiperidin-4-oneYield 58.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
16 °C

Procedure

To a stirred solution of benzylamine (5.2 mL, 47 mmol) in acetonitrile (30 mL) was added aqueous NaHCO3 solution (20 mL, 1.8 M, 36 mmol). After cooling to 16° C., the crude product obtained in step A (3.46 g, 32.9 mmol) dissolved in acetonitrile (30 mL) was added slowly over 40 minutes. After addition, the solution was heated to reflux for 1 h. The solvent was evaporated in vacuo to approximate 25 mL volume and ethyl acetate (60 mL) added. The resulting solution was stirred for 15 minutes. The organic layer was separated, washed with water (60 mL), dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue purified by flash column chromatography (SiO2, 8:1 to 7:3 hexanes/ethyl acetate) to give 1-benzyl-2-methylpiperidin-4-one (3.9 g, 54%) as a brown oil: 1H NMR (CDCl3, 300 MHz) δ 7.39-7.26 (m, 5H), 3.96 (d, J=13.5 Hz, 1H), 3.45 (d, J=13.2 Hz, 1H), 3.03-2.95 (m, 2H), 2.56-2.51 (m, 2H), 2.39-2.31 (m, 2H), 2.28-2.24 (m, 1H), 1.17 (d, J=6.3 Hz, 3H).

Workup

  1. additionwas added slowly over 40 minutes
  2. additionAfter addition
  3. temperaturethe solution was heated
  4. temperatureto reflux for 1 h
  5. customThe solvent was evaporated in vacuo to approximate 25 mL volume and ethyl acetate (60 mL)
  6. additionadded
  7. customThe organic layer was separated
  8. washwashed with water (60 mL)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationThe filtrate was concentrated in vacuo
  12. customthe residue purified by flash column chromatography (SiO2, 8:1 to 7:3 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-28288d7bb6cc41208926238e3c0b3537
Source dataset
uspto-grants-2015_06
Patent number
US09067949B2

Reaction notes

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