Sodium hydride → Tert-butyl 4-((4-methyl-2-oxopiperazin-1-yl)methyl)piperidine-1-carboxylate

HRID 524908Notes

Reaction equation

HRID 524908 reaction equation
[H-].[Na+].[CH3:3][N:4]1[CH2:9][CH2:8][NH:7][C:6](=[O:10])[CH2:5]1.CS(O[CH2:16][CH:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1)(=O)=O>CN(C=O)C>[CH3:3][N:4]1[CH2:9][CH2:8][N:7]([CH2:16][CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:27])([CH3:29])[CH3:28])=[O:24])[CH2:19][CH2:18]2)[C:6](=[O:10])[CH2:5]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2765838Tert-butyl 4-(methylsulfonyloxymethyl)piperidine-1-carboxylateHCID 137042831-Methyl-3-oxopiperazine

Product 1

HCID 86720963Tert-butyl 4-((4-methyl-2-oxopiperazin-1-yl)methyl)piperidine-1-carboxylateYield 20%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A 60% dispersion of sodium hydride (84.55 mg, 2.114 mmol) was added to a stirred solution of 4-methylpiperazin-2-one (241.3 mg, 2.114 mmol) in DMF (10 mL) and the reaction stirred at ambient temperature for 30 minutes. Tert-butyl 4-(methylsulfonyloxymethyl)piperidine-1-carboxylate (477 mg, 1.626 mmol) in DMF (5 mL) was added dropwise and the reaction stirred at ambient temperature for a further 92 hours then at 50° C. for a further 20 hours. The reaction was cooled to ambient temperature, quenched by the addition of water and the mixture extracted with EtOAc (×3). The combined organic extracts were washed with brine (×3), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion, 40 g column, eluting with 0 to 10% MeOH/DCM, loaded in DCM) to give tert-butyl 4-((4-methyl-2-oxopiperazin-1-yl)methyl)piperidine-1-carboxylate product as a colourless oil (99 mg, 20% Yield). MS (ES+) 312.2.

Workup

  1. stirringthe reaction stirred at ambient temperature for a further 92 hours
  2. waitat 50° C. for a further 20 hours
  3. temperatureThe reaction was cooled to ambient temperature
  4. customquenched by the addition of water
  5. extractionthe mixture extracted with EtOAc (×3)
  6. washThe combined organic extracts were washed with brine (×3)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by column chromatography (ISCO Companion, 40 g column, eluting with 0 to 10% MeOH/DCM, loaded in DCM)

Sources & evidence

ORD record
ord-e6560f5bd69e4ce6a8b7d59612386914
Source dataset
uspto-grants-2016_05
Patent number
US09340546B2

Reaction notes

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