2,4-Dichlorobenzaldehyde → 1-(3-Chloro-2-fluoro-phenyl)-5-(2,4-dichloro-phenyl)-3-hydroxy-4-isobutyryl-1,5-dihydro-pyrrol-2-one

HRID 869050Notes

Reaction equation

HRID 869050 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]=[C:17]([Cl:19])[CH:16]=[CH:15][C:12]=1[CH:13]=O.[Na].C([O:23][C:24](=O)[C:25](=[O:32])[CH2:26][C:27](=[O:31])[CH:28]([CH3:30])[CH3:29])C>C1(C)C=CC=CC=1.O1CCOCC1.C(O)(=O)C.CCOC(C)=O.O>[Cl:1][C:2]1[C:3]([F:9])=[C:4]([N:5]2[CH:13]([C:12]3[CH:15]=[CH:16][C:17]([Cl:19])=[CH:18][C:11]=3[Cl:10])[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

10

Reactant 4

HCID 134042,4-DichlorobenzaldehydeHCID 750143-Chloro-2-fluoroanilineHCID 3017501Ethyl 5-methyl-2,4-dioxohexanoateHCID 5360545Sodium

Product 1

HCID 896112721-(3-Chloro-2-fluoro-phenyl)-5-(2,4-dichloro-phenyl)-3-hydroxy-4-isobutyryl-1,5-dihydro-pyrrol-2-oneYield 50.7%

Reagents, catalysts & solvents 5

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 3-chloro-2-fluoro-aniline (428 mg, 2.94 mmol) and 2,4-dichloro-benzaldehyde (515 mg, 2.94 mmol) was heated to 110° C., stirred for 4 h, allowed to cool to rt, and diluted with toluene (5 mL). A solution of the sodium salt of 5-methyl-2,4-dioxo-hexanoic acid ethyl ester (615 mg, 2.94 mmol) in dioxane (5 mL) and acetic acid (0.17 mL) were added. The resulting mixture was refluxed for 15 h, allowed to cool to rt and diluted with EtOAc and water. The aqueous layer was separated and extracted with EtOAc. 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→95:5) to provide 660 mg of the title compound. tR: 1.40 min (LC-MS 1); ESI-MS: 443.8 [M+H]+ (LC-MS 1).

Workup

  1. temperatureto cool to rt
  2. temperatureThe resulting mixture was refluxed for 15 h
  3. temperatureto cool to rt
  4. customThe aqueous layer was separated
  5. extractionextracted with EtOAc
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by silica gel column chromatography (CH2Cl2/MeOH, 1:0→95:5)

Sources & evidence

ORD record
ord-7ef252c3ad9d433ab4b10ed6631c55cd
Source dataset
uspto-grants-2015_03
Patent number
US08969341B2

Reaction notes

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