Hydrochloric Acid → 1-benzyl-N-methylpiperidin-4-amine

HRID 1602136Notes

Reaction equation

HRID 1602136 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN.Cl.O1CCOCC1.[BH3-][C:25]#[N:26].[Na+].[OH-].[Na+]>CO.O>[CH3:25][NH:26][CH:11]1[CH2:12][CH2:13][N:8]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:9][CH2:10]1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 6329MethylamineHCID 14798Sodium HydroxideHCID 192201-Benzyl-4-piperidoneHCID 312751,4-DioxaneHCID 5003444Sodium cyanoborohydride

Product 1

HCID 41361281-benzyl-N-methylpiperidin-4-amineYield 86.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of 1-benzyl-4-piperidone (1.9 g, 10 mmol) in MeOH (10 ml) were added methylamine (8 ml, 16 mmol) and 3 Å molecular sieves. After stirring at RT for 1 h, the reaction was cooled in an ice-bath and 4 N HCl in dioxane (2.5 ml, 10 mmole) and NaCNBH3 (1.2 g, 20 mmol) were added. The reaction was stirred at RT overnight. After the reaction was complete, H2O was added the pH was adjusted to 10 with 50% NaOH solution. The product was extracted with EtOAc (100 ml, 3×) from aqueous solution and combined. The combined organic solution was washed with brine, dried over MgSO4, filtered and concentrated to give an oil which was purified by silica flash chromatography, eluting with 8% saturated NH3 /MeOH in CH2Cl2 to give 4-methylamino-1-benzyl piperidine (1.77 g, 8.66 mmol, 86%). FAB Mass [M+1]+35Cl 205.

Workup

  1. temperaturethe reaction was cooled in an ice-bath
  2. stirringThe reaction was stirred at RT overnight
  3. extractionThe product was extracted with EtOAc (100 ml, 3×) from aqueous solution
  4. washThe combined organic solution was washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give an oil which
  9. customwas purified by silica flash chromatography
  10. washeluting with 8% saturated NH3 /MeOH in CH2Cl2

Sources & evidence

ORD record
ord-7d36503237c7415ca7f6abd2a1fba18e
Source dataset
uspto-grants-1999_11
Patent number
US05981520

Reaction notes

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