Acetic Acid → 1-benzyl-N,N-dimethylpiperidin-4-amine dihydrochloride

HRID 1042680Notes

Reaction equation

HRID 1042680 reaction equation
N[CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.[BH3-][C:16]#[N:17].[Na+].[CH3:19]C(O)=O.C=O.C(Cl)[Cl:26]>CO>[ClH:26].[ClH:26].[CH2:8]([N:5]1[CH2:6][CH2:7][CH:2]([N:17]([CH3:16])[CH3:19])[CH2:3][CH2:4]1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 712FormaldehydeHCID 6344DichloromethaneHCID 4158521-Benzyl-4-piperidylamineHCID 5003444Sodium cyanoborohydride

Product 1

HCID 231533931-benzyl-N,N-dimethylpiperidin-4-amine dihydrochloride

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a mixture of 4-amino-1-benzyl piperidine (5.0 g, 26 mmol), NaBH3CN (3.3 g, 53 mmol), AcOH (7.5 ml, 132 mmol) in 130 ml MeOH at 0° C. under nitrogen was added formaldehyde (37 wt % in water, 5.3 mL) as a solution in 15 ml MeOH slowly dropwise via a pressure-equalized addition funnel over 15 min. The resulting clear solution was allowed to warm to room temperature and was allowed to stir for approximately 60 h. The reaction was quenched by the addition of 20 ml saturated aqueous potassium carbonate. The mixture was concentrated in vacuo, and water and EtOAc was added. The organic layer was removed, and the aqueous layer was extracted twice with EtOAc. The combined organic layers were dried with Na2SO4, filtered, and concentrated to give a cloudy oil, which was dissolved in methylene chloride and filtered through a fritted funnel. The solvent was removed to give a waxy solid, which was purified by silica gel chromatography (MC/MeOH/conc. NH4OH). The resulting material was dissolved in diethyl ether, cooled to 0° C. and treated with 20 ml 4N HCl in dioxane. The solvent was removed in vacuo to give the desired product as a white solid. MS (m/z): 219.1 (M+H)+. Calc'd for C14H22N2: 218.34.

Workup

  1. customThe reaction was quenched by the addition of 20 ml saturated aqueous potassium carbonate
  2. concentrationThe mixture was concentrated in vacuo, and water and EtOAc
  3. additionwas added
  4. customThe organic layer was removed
  5. extractionthe aqueous layer was extracted twice with EtOAc
  6. dry with materialThe combined organic layers were dried with Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a cloudy oil, which
  10. filtrationfiltered through a fritted funnel
  11. customThe solvent was removed
  12. customto give a waxy solid, which
  13. customwas purified by silica gel chromatography (MC/MeOH/conc. NH4OH)
  14. dissolutionThe resulting material was dissolved in diethyl ether
  15. temperaturecooled to 0° C.
  16. additiontreated with 20 ml 4N HCl in dioxane
  17. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-2e252685b4ef4e64adcfdf125f4bce6e
Source dataset
uspto-grants-2013_10
Patent number
US08557996B2

Reaction notes

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