Acetic Acid → Tert-butyl 4-(4-ethylpiperazin-1-yl)piperidine-1-carboxylate

HRID 2368196Notes

Reaction equation

HRID 2368196 reaction equation
[CH2:1]([N:3]1[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1)[CH3:2].O=[C:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]1.C(O)(=O)C.C(O[BH3-])(=O)C.[Na+].[OH-].[Na+]>C(O)C>[CH2:1]([N:3]1[CH2:8][CH2:7][N:6]([CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)[CH2:5][CH2:4]1)[CH3:2]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 791961-EthylpiperazineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 23670382Sodiumacetoxyborohydride

Product 1

HCID 67048572Tert-butyl 4-(4-ethylpiperazin-1-yl)piperidine-1-carboxylateYield 53%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

29.2 g (256 mmol) of N-ethylpiperazine were introduced with 50.0 g (256 mmol) of tert-butyl 4-oxopiperidine-1-carboxylate (corresponds to 1-Boc-4-piperidone) into 800 ml of ethanol while cooling in ice. 15.4 g (256 mmol) of glacial acetic acid were added. Then 16.1 g (256 mmol) of sodium acetoxyborohydride were added in portions to the cooled reaction mixture. Initially slight gas formation was observed and, after addition of ⅔ of the reducing agent, foam formation was observed. The reaction mixture was stirred at room temperature overnight. The reaction solution was worked up by adding 200 ml of 2N of sodium hydroxide solution while cooling, distilling out the solvent ethanol and diluting the remaining reaction mixture with water. It was extracted with diethyl ether (2×) and was washed with saturated sodium chloride solution (1×), and the combined organic phases were dried over magnesium sulfate and filtered, and the solvent was removed in vacuo. The crude title compound was obtained as a yellow oil which was then chromatographed on a 4 l suction funnel filled with silica gel using dichloromethane and 10% methanol as eluent. In total, 40 g (135 mmol, 53%) of tert-butyl 4-(4-ethylpiperazin-1-yl)piperidine-1-carboxylate were obtained.

Workup

  1. temperaturewhile cooling in ice
  2. additionafter addition of ⅔ of the reducing agent, foam formation
  3. temperaturewhile cooling
  4. distillationdistilling out the solvent ethanol
  5. additiondiluting
  6. customthe remaining reaction mixture with water
  7. extractionIt was extracted with diethyl ether (2×)
  8. washwas washed with saturated sodium chloride solution (1×)
  9. dry with materialthe combined organic phases were dried over magnesium sulfate
  10. filtrationfiltered
  11. customthe solvent was removed in vacuo
  12. customThe crude title compound was obtained as a yellow oil which
  13. customwas then chromatographed on a 4 l suction funnel
  14. additionfilled with silica gel

Sources & evidence

ORD record
ord-226768ed684c4ccf92c298a5ed831f3d
Source dataset
uspto-grants-2014_04
Patent number
US08703774B2

Reaction notes

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