1-(Trimethylsilyl)pyrrolidin-2-one → 3-(2-Chloropyrid 5-yl-methyl)-pyrrolid-2-one

HRID 1003925Notes

Reaction equation

HRID 1003925 reaction equation
C([N-]C(C)C)(C)C.[Li+].C[Si](C)(C)[N:11]1[CH2:15][CH2:14][CH2:13][C:12]1=[O:16].[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26]Cl)=[CH:22][N:21]=1>C1CCCCC1.O1CCCC1>[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][CH:13]2[CH2:14][CH2:15][NH:11][C:12]2=[O:16])=[CH:22][N:21]=1

Participants

6

Reactant 3

HCID 844611-(Trimethylsilyl)pyrrolidin-2-oneHCID 1554792-Chloro-5-(chloromethyl)pyridineHCID 2724682Lithium diisopropylamide

Product 1

HCID 187597883-(2-Chloropyrid 5-yl-methyl)-pyrrolid-2-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8078CyclohexaneSolvent

Procedure

Under a nitrogen atmosphere at a temperature of from -78° C. to -60° C., 180 ml of a 1.5 molar solution of lithium diisopropylamide (LDA) in cyclohexane are added dropwise to 31.4 g of N-trimethylsilylpyrrolid-2-one in 150 ml of tetrahydrofuran (THF) and the reaction mixture is stirred at the same temperature for a further one hour. Then, at from -78° C. to -60° C., 25.5 g of 2-chloro-5-chloromethylpyridine in 40 ml of THF are added, and the mixture is stirred for a further 16 hours at that temperature and then for a further three hours at room temperature. The reaction mixture is poured onto a mixture of ice/water and extracted with ethyl acetate, and the organic phase is separated off. The ethyl acetate phase is dried over sodium sulfate and concentrated to dryness by evaporation in vacuo. The residue is purified on silica gel using ethyl acetate/hexane (7:1) as eluant. The title compound having a melting point of 117-118° C. (compound 1.3) is obtained.

Workup

  1. stirringthe mixture is stirred for a further 16 hours at that temperature
  2. waitfor a further three hours at room temperature
  3. extractionextracted with ethyl acetate
  4. customthe organic phase is separated off
  5. dry with materialThe ethyl acetate phase is dried over sodium sulfate
  6. concentrationconcentrated to dryness by evaporation in vacuo
  7. customThe residue is purified on silica gel
  8. customis obtained

Sources & evidence

ORD record
ord-abc11c9087ec4bbda0b44656b3fcde10
Source dataset
uspto-grants-2000_04
Patent number
US06048824

Reaction notes

Loading…