Acetic Acid → Piperidine, 1-methyl-4-phenyl-

HRID 887583Notes

Reaction equation

HRID 887583 reaction equation
[C:1]1([CH:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C=O.[BH3-][C:16]#N.[Na+].CC(O)=O>CC#N.O.C(Cl)Cl>[CH3:16][N:10]1[CH2:9][CH2:8][CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:12][CH2:11]1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 698734-PhenylpiperidineHCID 5003444Sodium cyanoborohydride

Product 1

HCID 202391Piperidine, 1-methyl-4-phenyl-

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirring mixture at RT of 4-phenylpiperidine (5.24 g, 32.48 mmol) in CH3CN (95 ml) was added a 37% solution of HCHO in H2O (13 ml). To this mixture was added NaCNBH3 (3.27 g, 51.97 mmol). AcOH was added dropwise every 10 min over the next h to maintain the reaction pH near 7. The reaction volume was then reduced in vacuo. The reaction mix was diluted with CH2Cl2 and washed with 2N NaOH and then brine. The crude was concentrated in vacuo and eluted through a silica gel column with 10% MeOH/CH2Cl2. The 1-methyl-4-phenylpiperidine was concentrated in vacuo, yielding a clear oil.

Workup

  1. temperatureto maintain
  2. customthe reaction pH near 7
  3. additionThe reaction mix
  4. washwashed with 2N NaOH
  5. concentrationThe crude was concentrated in vacuo
  6. washeluted through a silica gel column with 10% MeOH/CH2Cl2
  7. concentrationThe 1-methyl-4-phenylpiperidine was concentrated in vacuo
  8. customyielding a clear oil

Sources & evidence

ORD record
ord-d86961f2651740bc91844a0378958fe9
Source dataset
uspto-grants-2012_08
Patent number
US08247430B2

Reaction notes

Loading…