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

HRID 869049Notes

Reaction equation

HRID 869049 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)=[CH:13][CH:12]=1.[Na].C([O:22][C:23](=O)[C:24](=[O:31])[CH2:25][C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])C.C(O)(=O)C>C1(C)C=CC=CC=1.O1CCOCC1.CCOC(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][CH:13]=3)[C:25]([C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])=[C:24]([OH:31])[C:23]2=[O:22])[CH:6]=[CH:7][CH:8]=1

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 77264-ChlorobenzaldehydeHCID 750143-Chloro-2-fluoroanilineHCID 3017501Ethyl 5-methyl-2,4-dioxohexanoateHCID 5360545Sodium

Product 1

HCID 896024311-(3-Chloro-2-fluoro-phenyl)-5-(4-chloro-phenyl)-3-hydroxy-4-isobutyryl-1,5-dihydro-pyrrol-2-oneYield 48.3%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 3-chloro-2-fluoro-aniline (10.9 g, 75 mmol) and 4-chloro-benzaldehyde (10.0 g, 71 mmol) was heated to 120° C., stirred for 18 h, allowed to cool to rt, and diluted with toluene (50 mL). A mixture of the sodium salt of 5-methyl-2,4-dioxo-hexanoic acid ethyl ester (14.8 g, 71 mmol) in dioxane (50 mL) and acetic acid (4.1 mL, 71 mmol) was added. The resulting mixture was refluxed for 18 h, allowed to cool to rt, diluted with EtOAc, and washed twice with an aqueous solution of NaHCO3 and brine. The crude product, obtained after drying and concentration, was triturated with EtOAc/hexane to provide 14 g of the title compound. tR: 5.23 min (HPLC 1); ESI-MS: 408 [M+H]+ (LC-MS1).

Workup

  1. temperatureto cool to rt
  2. additionwas added
  3. temperatureThe resulting mixture was refluxed for 18 h
  4. temperatureto cool to rt
  5. washwashed twice with an aqueous solution of NaHCO3 and brine
  6. customThe crude product, obtained
  7. customafter drying
  8. concentrationconcentration
  9. customwas triturated with EtOAc/hexane

Sources & evidence

ORD record
ord-7efad27c4cae4c95b1355cb632814a3e
Source dataset
uspto-grants-2015_03
Patent number
US08969341B2

Reaction notes

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