2-Pyrrolidone → 1-(4-Chloro-2-fluorophenyl)pyrrolidin-2-one

HRID 40218

Reaction equation

HRID 40218 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](I)=[C:4]([F:9])[CH:3]=1.[NH:10]1[CH2:14][CH2:13][CH2:12][C:11]1=[O:15].[C@@H]1(N)CCCC[C@H]1N.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>[Cu]I>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:10]2[CH2:14][CH2:13][CH2:12][C:11]2=[O:15])=[C:4]([F:9])[CH:3]=1

Participants

7

Reactant 5

HCID 120252-PyrrolidoneHCID 312751,4-DioxaneHCID 438061,2-Diaminocyclohexane, trans-HCID 62657Potassium Phosphate, TribasicHCID 27365624-Chloro-2-fluoro-1-iodobenzene

Product 1

HCID 576910901-(4-Chloro-2-fluorophenyl)pyrrolidin-2-oneYield 108.4%

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Procedure

A 100 mL sealed tube was charged with 4-chloro-2-fluoro-1-iodobenzene (0.498 ml, 3.90 mmol), pyrrolidin-2-one (0.598 ml, 7.80 mmol), (1R,2R)-cyclohexane-1,2-diamine (0.0703 ml, 0.585 mmol), potassium phosphate (1.66 g, 7.80 mmol), copper (I) iodide (0.0223 g, 0.117 mmol), and 1,4-dioxane (4.00 ml, 46.8 mmol), then flushed with argon, sealed, and placed in a 110° C. oil bath for 17 hours. The reaction mixture was filtered through a pad of silica gel, eluting with EtOAc and DCM, then the filtrate was concentrated to yield a brown oil This was purified by column chromatography using a 40 g ISCO column, eluting with a gradient of 3-5% MeOH/DCM over 30 minutes to give 1-(4-chloro-2-fluorophenyl)pyrrolidin-2-one (0.903 g, 108% yield) as a yellow solid.

Workup

  1. customA 100 mL sealed tube
  2. customflushed with argon
  3. customsealed
  4. customplaced in a 110° C.
  5. customfor 17 hours
  6. filtrationThe reaction mixture was filtered through a pad of silica gel
  7. washeluting with EtOAc and DCM
  8. concentrationthe filtrate was concentrated
  9. customto yield a brown oil
  10. customThis was purified by column chromatography
  11. washeluting with a gradient of 3-5% MeOH/DCM over 30 minutes

Sources & evidence

ORD record
ord-95c447c9de33441fbd973a9a7a334c36
Source dataset
uspto-grants-2013_09
Patent number
US08524900B2

Linked notes

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