Acetic Acid → Phenylmethyl 4-[(cyclopropylamino)methyl]-1-piperidinecarboxylate

HRID 220838Notes

Reaction equation

HRID 220838 reaction equation
[CH:1]1([NH2:4])[CH2:3][CH2:2]1.C(O)(=O)C.[CH2:9]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([CH:25]=O)[CH2:21][CH2:20]1)=[O:18])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C([BH3-])#N.[Na+]>CO>[CH2:9]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([CH2:25][NH:4][CH:1]2[CH2:3][CH2:2]2)[CH2:21][CH2:20]1)=[O:18])[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 69828CyclopropylamineHCID 2776272Benzyl 4-formylpiperidine-1-carboxylateHCID 5003444Sodium cyanoborohydride

Product 1

HCID 57555432Phenylmethyl 4-[(cyclopropylamino)methyl]-1-piperidinecarboxylateYield 47%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Cyclopropylamine (1.4 g, 24.4 mmol) and acetic acid (0.5 ml) were added to a solution of 4-formyl-piperidine-1-carboxylic acid benzyl ester from Example E33.2 (5.5 g, 22.2 mmol) in methanol (49.5 ml) and the mixture was stirred for 1 h at room temperature. Sodium cyanoborohydride (1.84 g, 28.9 mmol) was added and the mixture was stirred for 20 h at room temperature under an inert atmosphere. Solvents were removed in vacuo and azeotroped with toluene. The residue was dissolved in EtOAC, washed with saturated NaHCO3 then brine, dried and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (eluant; 10% methanol:90% dichloromethane) to yield the title compound (3.0 g, 47%).

Workup

  1. stirringthe mixture was stirred for 20 h at room temperature under an inert atmosphere
  2. customSolvents were removed in vacuo
  3. customazeotroped with toluene
  4. dissolutionThe residue was dissolved in EtOAC
  5. washwashed with saturated NaHCO3
  6. dry with materialbrine, dried
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography on silica gel (eluant; 10% methanol:90% dichloromethane)

Sources & evidence

ORD record
ord-30e1b01a1f9340e798e77cc3cde53b73
Source dataset
uspto-grants-2012_06
Patent number
US08202858B2

Reaction notes

Loading…