Sodium hydride → 1-(4-Bromo-2,6-dichloro-benzyl)-3-piperidin-1-yl-pyrrolidin-2-one

HRID 1670841Notes

Reaction equation

HRID 1670841 reaction equation
[N:1]1([CH:7]2[CH2:11][CH2:10][NH:9][C:8]2=[O:12])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[Br:15][C:16]1[CH:17]=[C:18]([Cl:25])[C:19]([CH2:23]Br)=[C:20]([Cl:22])[CH:21]=1>CN(C=O)C.C(OCC)C>[Br:15][C:16]1[CH:17]=[C:18]([Cl:25])[C:19]([CH2:23][N:9]2[CH2:10][CH2:11][CH:7]([N:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)[C:8]2=[O:12])=[C:20]([Cl:22])[CH:21]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 576580133-Piperidin-1-yl-pyrrolidin-2-oneHCID 594744985-Bromo-2-(bromomethyl)-1,3-dichlorobenzene

Product 1

HCID 576580161-(4-Bromo-2,6-dichloro-benzyl)-3-piperidin-1-yl-pyrrolidin-2-oneYield 90.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

Treat a solution of 3-piperidin-1-yl-pyrrolidin-2-one (0.33 g, 1.96 mmol) in DMF (6 mL) with 60% sodium hydride (0.12 g, 3.00 mmol) and stir at room temperature for 15 minutes under N2. Cool the reaction to 0° C., treat with 5-bromo-2-(bromomethyl)-1,3-dichlorobenzene (0.70 g, 2.19 mmol), stir for 15 minutes at 0° C., warm to room temperature, and stir for 3 hours under N2. Quench the reaction with water and dilute with diethyl ether. Dry the organic layer (Na2SO4), remove the solvent in vacuo to afford crude product, and purify with a 0 to 5% methanol in CH2Cl2 gradient to afford 0.718 g (90%) of the titled product. Rf=0.29 (9/1 CH2Cl2/methanol). ES MS (m/z): 407 (M+).

Workup

  1. temperatureCool
  2. customthe reaction to 0° C.
  3. stirringstir for 15 minutes at 0° C.
  4. temperaturewarm to room temperature
  5. stirringstir for 3 hours under N2
  6. customQuench
  7. customthe reaction with water
  8. dry with materialDry the organic layer (Na2SO4)
  9. customremove the solvent in vacuo
  10. customto afford crude product
  11. custompurify with a 0 to 5% methanol in CH2Cl2 gradient

Sources & evidence

ORD record
ord-aeb6cb6781fb4c83b33dc3f71cb4614b
Source dataset
uspto-grants-2011_08
Patent number
US07994176B2

Reaction notes

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