2-Pyrrolidone → HCID 86682961, compound

HRID 1497107Notes

Reaction equation

HRID 1497107 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][C:2]1=[O:6].[H-].[Na+].[CH2:9]([O:11][C:12]([C:14]1[C:15](Cl)=[N:16][C:17]2[C:22]([C:23]=1[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[CH:21][C:20]([Cl:30])=[CH:19][CH:18]=2)=[O:13])[CH3:10]>C1COCC1>[CH2:9]([O:11][C:12]([C:14]1[C:15]([N:1]2[CH2:5][CH2:4][CH2:3][C:2]2=[O:6])=[N:16][C:17]2[C:22]([C:23]=1[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[CH:21][C:20]([Cl:30])=[CH:19][CH:18]=2)=[O:13])[CH3:10]

Participants

5

Reactant 3

HCID 120252-PyrrolidoneHCID 24758Sodium hydrideHCID 1714247Ethyl 2,6-dichloro-4-phenylquinoline-3-carboxylate

Product 1

HCID 86682961HCID 86682961, compoundYield 7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of pyrrolidin-2-one (0.054 ml, 0.69 mmol) in THF in a microwave vessel under nitrogen, was added NaH (28 mg, 0.69 mmol) portion wise at 25° C. The reaction mixture was stirred for 30 min followed by the addition of a solution of 2,6-dichloro-4-phenyl-quinoline-3-carboxylic acid ethyl ester (prepared as described in example 11 step B, 200 mg, 0.58 mmol) in 2 ml THF at 25° C. Then the resulting reaction mixture was stirred for 1 h at 60° C. in a microwave. After cooling, reaction mixture was quenched with saturated aqueous NH4Cl solution and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to afford a crude residue which was purified by flash column chromatography (eluting with 20% ethyl acetate in hexane) to obtain 6-chloro-2-(2-oxo-pyrrolidin-1-yl)-4-phenyl-quinoline-3-carboxylic acid ethyl ester (15 mg, 7%) as an off white solid. LC-MS: 395 (M+H)+.

Workup

  1. customThen the resulting reaction mixture
  2. stirringwas stirred for 1 h at 60° C. in a microwave
  3. temperatureAfter cooling
  4. customreaction mixture
  5. customwas quenched with saturated aqueous NH4Cl solution
  6. extractionextracted with ethyl acetate
  7. washThe organic layer was washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated in vacuo
  10. customto afford a crude residue which
  11. customwas purified by flash column chromatography (eluting with 20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-24db202f320147d89db48e1de9e56535
Source dataset
uspto-grants-2015_12
Patent number
US09199938B2

Reaction notes

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