Acetic Acid → 1-methyl-N-[(4-methylphenyl)methyl]piperidin-4-amine

HRID 354155Notes

Reaction equation

HRID 354155 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][C:5](=O)[CH2:4][CH2:3]1.[CH3:9][C:10]1[CH:17]=[CH:16][C:13]([CH2:14][NH2:15])=[CH:12][CH:11]=1.C(O)(=O)C.[BH3-]C#N.[Na+]>CO>[CH3:9][C:10]1[CH:17]=[CH:16][C:13]([CH2:14][NH:15][CH:5]2[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]2)=[CH:12][CH:11]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 660354-MethylbenzylamineHCID 740491-Methyl-4-piperidoneHCID 5003444Sodium cyanoborohydride

Product 1

HCID 119938621-methyl-N-[(4-methylphenyl)methyl]piperidin-4-amineYield 93%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent3×

Procedure

1-Methyl-4-piperidone (1.13 g, 10 mmol) was dissolved in 20 ml of methanol and added to a 100 ml flask. 4-Methylbenzylamine (1.21 g, 10 mmol) in 10 ml of methanol was added. Acetic acid (˜1.5 ml) was added until pH˜5. NaCNBH3 (1.26 g, 20 mmol) was slowly added. After 20 hrs magnetic stirring methanol was partly removed on Rotavapor (40° C.). Dichloromethane, water and 2M NaOH were added until pH˜10. The phases were separated and aq. phase was extracted twice with dichloromethane. The combined organic phases were washed with brine and dried over MgSO4. Concentration on Rotavapor (40° C.) yielded 2.06 g crude (93%) 47AKU-5. TLC (20% methanol in dichloromethane): Rf=0.3. HPLC-MS (Method A): M+=219.1 (UV/MS(%)=89/98).

Workup

  1. additionadded to a 100 ml flask
  2. customwas partly removed on Rotavapor (40° C.)
  3. additionDichloromethane, water and 2M NaOH were added until pH˜10
  4. customThe phases were separated
  5. extractionaq. phase was extracted twice with dichloromethane
  6. washThe combined organic phases were washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationConcentration on Rotavapor (40° C.)

Sources & evidence

ORD record
ord-421cb6d3462c40829236eb193d350e7c
Source dataset
uspto-grants-2004_06
Patent number
US06756393B2

Reaction notes

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