Acetic Acid → 1-Methyl-N-phenylpiperidin-4-amine

HRID 1922380Notes

Reaction equation

HRID 1922380 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:8][N:9]1[CH2:14][CH2:13][C:12](=O)[CH2:11][CH2:10]1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[OH-].[Na+]>ClCCCl>[CH3:8][N:9]1[CH2:14][CH2:13][CH:12]([NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:11][CH2:10]1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 6115AnilineHCID 14798Sodium HydroxideHCID 740491-Methyl-4-piperidoneHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 896421-Methyl-N-phenylpiperidin-4-amineYield 98%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of aniline (2.0 g, 1.95 mL, 21.475 mmol), N-methyl-4-piperidone (2.64 mL, 21.475 mmol) and AcOH (1.21 mL, 21.475 mmol) in dry 1,2-dichloroethane (20 mL) was treated with NaBH(OAc)3 (6.82 g, 32.213 mmol) at 0° C. The reaction was brought to room temperature and stirred for over night (16 h). The reaction was basified with 1 N NaOH solution (40 mL) and product was extracted into CH2Cl2 (2×25 mL). The combined CH2Cl2 layer was washed with brine (15 mL) and dried (Na2SO4). Solvent was evaporated and crude was purified by column chromatography (2 M NH3 in MeOH:CH2Cl2, 5:95) to obtain compound 1-methyl-N-phenylpiperidin-4-amine (4.0 g, 98%) as a solid. 1H NMR (DMSO-d6) δ: 1.29-1.42 (m, 2H), 1.82-1.88 (m, 2H), 1.93-2.02 (m, 2H), 2.15 (s, 3H), 2.68-2.74 (m, 2H), 3.08-3.18 (m, 1H), 5.36 (d, 1H, J=8.1 Hz), 6.47 (t, 1H, J=7.2 Hz), 6.54 (d, 2H, J=7.8 Hz), 7.03 (t, 2H, J=7.2 Hz); ESI-MS (m/z, %) 191 (MH+, 100).

Workup

  1. customwas brought to room temperature
  2. extractionwas extracted into CH2Cl2 (2×25 mL)
  3. washThe combined CH2Cl2 layer was washed with brine (15 mL)
  4. dry with materialdried (Na2SO4)
  5. customSolvent was evaporated
  6. customcrude was purified by column chromatography (2 M NH3 in MeOH:CH2Cl2, 5:95)

Sources & evidence

ORD record
ord-b681b2b08d6d42508308ec06a4612382
Source dataset
uspto-grants-2012_05
Patent number
US08173813B2

Reaction notes

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