3-Chloro-2-fluoroaniline → 1-(3-Chloro-2-fluoro-phenyl)-5-(4-chloro-2-methyl-phenyl)-3-hydroxy-4-isobutyryl-1,5-dihydro-pyrrol-2-one

HRID 869048Notes

Reaction equation

HRID 869048 reaction equation
[Cl:1][C:2]1[C:3]([F:9])=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].[Cl:10][C:11]1[CH:18]=[CH:17][C:14]([CH:15]=O)=[C:13]([CH3:19])[CH:12]=1.[Na].C([O:23][C:24](=O)[C:25](=[O:32])[CH2:26][C:27](=[O:31])[CH:28]([CH3:30])[CH3:29])C>C(O)(=O)C.O>[Cl:1][C:2]1[C:3]([F:9])=[C:4]([N:5]2[CH:15]([C:14]3[CH:17]=[CH:18][C:11]([Cl:10])=[CH:12][C:13]=3[CH3:19])[C:26]([C:27](=[O:31])[CH:28]([CH3:30])[CH3:29])=[C:25]([OH:32])[C:24]2=[O:23])[CH:6]=[CH:7][CH:8]=1

Participants

7

Reactant 4

HCID 750143-Chloro-2-fluoroanilineHCID 27576584-Chloro-2-methylbenzaldehydeHCID 3017501Ethyl 5-methyl-2,4-dioxohexanoateHCID 5360545Sodium

Product 1

HCID 896111051-(3-Chloro-2-fluoro-phenyl)-5-(4-chloro-2-methyl-phenyl)-3-hydroxy-4-isobutyryl-1,5-dihydro-pyrrol-2-oneYield 21%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

A mixture of 3-chloro-2-fluoro-aniline (0.70 g, 4.8 mmol), 4-chloro-2-methyl-benzaldehyde (0.74 g, 4.8 mmol) and the sodium salt of 5-methyl-2,4-dioxo-hexanoic acid ethyl ester (1.0 g, 4.8 mmol) in acetic acid (6 mL) was refluxed for 3 h. The reaction mixture was diluted with water and extracted twice with ethyl acetate. The combined organic extracts were washed with brine, dried (Na2SO4), filtered, and concentrated. The residue was purified by silica gel column chromatography (CH2Cl2/MeOH, 1:0→9:1), followed by crystallization from EtOAc/hexane, to provide 426 mg of the title compound. tR: 5.47 min (HPLC 1); ESI-MS: 422 [M+H]+ (LC-MS 1).

Workup

  1. extractionextracted twice with ethyl acetate
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography (CH2Cl2/MeOH, 1:0→9:1)
  7. customfollowed by crystallization from EtOAc/hexane

Sources & evidence

ORD record
ord-d349d89122a74a1b8e361779eaffe1f3
Source dataset
uspto-grants-2015_03
Patent number
US08969341B2

Reaction notes

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