Cesium carbonate → 2-Fluoro-3-(2-oxopyrrolidin-1-yl)-5-trifluoromethylbenzoic Acid Methyl Ester

HRID 1612443Notes

Reaction equation

HRID 1612443 reaction equation
[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[C:6](Br)[C:5]=1[F:15].C(=O)([O-])[O-].[Cs+].[Cs+].[NH:23]1[CH2:27][CH2:26][CH2:25][C:24]1=[O:28].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.COC(=O)C1C=C(C(F)(F)F)C=C(Cl)C=1N1CCCC1=O>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[C:6]([N:23]2[CH2:27][CH2:26][CH2:25][C:24]2=[O:28])[C:5]=1[F:15]

Participants

8

Reactant 5

HCID 10796Cesium carbonateHCID 120252-PyrrolidoneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 69361010Methyl 3-bromo-2-fluoro-5-(trifluoromethyl)benzoateHCID 695899223-Chloro-2-(2-oxopyrrolidin-1-yl)-5-trifluoromethylbenzoic acid methyl ester

Product 1

HCID 695896852-Fluoro-3-(2-oxopyrrolidin-1-yl)-5-trifluoromethylbenzoic Acid Methyl Ester

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

3-Bromo-2-fluoro-5-trifluoromethylbenzoic acid methyl ester (500 mg, 1.95 mmol)), caesium carbonate (950 mg, 2.92 mmol), pyrrolidin-2-one (248 mg, 2.92 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (68 mg, 0.117 mmol) and tris(dibenzylideneacetone)dipalladium (0) (36 mg, 0.039 mmol) were refluxed under argon in dioxane (7 ml) for 18 h. After cooling, the mixture was filtered and evaporated in vacuo. Column chromatography on silica gel eluting with a gradient of 20–50% ethyl acetate in hexane gave a mixture of D24 and 3-chloro-2-(2-oxopyrrolidin-1-yl)-5-trifluoromethylbenzoic acid methyl ester (195 mg).

Workup

  1. temperatureAfter cooling
  2. filtrationthe mixture was filtered
  3. customevaporated in vacuo
  4. customColumn chromatography on silica gel eluting with a gradient of 20–50% ethyl acetate in hexane gave

Sources & evidence

ORD record
ord-1062ebf2599f40babd596cc640ecafcd
Source dataset
uspto-grants-2006_01
Patent number
US06992103B2

Reaction notes

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