Sodium hydride → Tert-butyl 4-[(1-benzylpiperidin-3-yl)methyl]-3-oxopiperazine-1-carboxylate

HRID 2371138Notes

Reaction equation

HRID 2371138 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][C:10](=[O:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].CC1C=CC(S(O[CH2:28][CH:29]2[CH2:34][CH2:33][CH2:32][N:31]([CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[CH2:30]2)(=O)=O)=CC=1>CN(C)C=O>[CH2:35]([N:31]1[CH2:32][CH2:33][CH2:34][CH:29]([CH2:28][N:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][C:10]2=[O:14])[CH2:30]1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

5

Reactant 3

HCID 24758Sodium hydride3×HCID 3157178Tert-butyl 3-oxopiperazine-1-carboxylateHCID 57656889(1-Benzylpiperidin-3-yl)methyl 4-methylbenzenesulfonate

Product 1

HCID 57656824Tert-butyl 4-[(1-benzylpiperidin-3-yl)methyl]-3-oxopiperazine-1-carboxylateYield 20%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of tert-butyl-3-oxopiperazine-1-carboxylate (250 mg) in dimethylformamide (10 mL) was added sodium hydride (55 mg) at room temperature under argon. The mixture was stirred at room temperature 15 minutes before a solution of (1-benzylpiperidin-3-yl)methyl 4-methylbenzenesulfonate (492 mg) in dimethylformamide (5 mL) was added. The mixture was stirred overnight at room temperature before sodium hydride (60 mg) was added and the mixture was stirred for 48 hours. A further quantity of sodium hydride (60 mg) was added and the mixture was stirred for 5 hours and then quenched by the addition of water. The mixture was then partitioned between water and ethyl acetate. The layers were separated and the organic layer washed twice with water and once with brine. The organic layer was then dried over sodium sulfate and evaporated. The residue was purified by silica column chromatography, eluting with a gradient of 0 to 70% ethyl acetate in hexane to give the title compound as a colourless oil (95 mg, 20%).

Workup

  1. additionwas added
  2. additionwas added
  3. stirringthe mixture was stirred for 5 hours
  4. customquenched by the addition of water
  5. customThe mixture was then partitioned between water and ethyl acetate
  6. customThe layers were separated
  7. washthe organic layer washed twice with water and once with brine
  8. dry with materialThe organic layer was then dried over sodium sulfate
  9. customevaporated
  10. customThe residue was purified by silica column chromatography
  11. washeluting with a gradient of 0 to 70% ethyl acetate in hexane

Sources & evidence

ORD record
ord-8050240b4ec646ca80f8e93b280bc786
Source dataset
uspto-grants-2014_04
Patent number
US08710224B2

Reaction notes

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