Piperazine → Tert-butyl 4-(piperazin-1-ylmethyl)piperidine-1-carboxylate

HRID 496627Notes

Reaction equation

HRID 496627 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]=O)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[NH:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.C(#N)C>[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][N:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

6

Reactant 3

HCID 4837PiperazineHCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 22321697Tert-butyl 4-(piperazin-1-ylmethyl)piperidine-1-carboxylateYield 125.8%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of 1-Boc-piperidine-4-carboxaldehyde (2.4 g, 11.3 mmol) in THF (60 mL) and acetonitrile (15 mL) was added piperazine (4.85 g, 56.3 mmol). After stirring for 5 h, sodium triacetoxyborohydride (2.87 g, 13.5 mmol) was added and the reaction was allowed to stir overnight. The next morning, the solvents were removed by rotary evaporation and the residue was dissolved in ethyl acetate, washed twice with satd aq. NaHCO3, followed by water, then dried over MgSO4, filtered and concentrated in vacuo. The residue was then chromatographed over silica gel, eluting with a step gradient of 2% through 15% (2 N ammonia/methanol) in dichloromethane. The product containing fractions were combined and concentrated in vacuo to give 4.03 g (48%) of the title compound.

Workup

  1. stirringto stir overnight
  2. customThe next morning, the solvents were removed by rotary evaporation
  3. dissolutionthe residue was dissolved in ethyl acetate
  4. washwashed twice with satd aq. NaHCO3
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was then chromatographed over silica gel
  9. washeluting with a step gradient of 2% through 15% (2 N ammonia/methanol) in dichloromethane
  10. additionThe product containing fractions
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6a6a7affc65a43ef9d31035675e8db96
Source dataset
uspto-grants-2005_09
Patent number
US06946467B2

Reaction notes

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