Cesium carbonate → [6-Fluoro-4-(4-methanesulfonyl-phenylamino)-naphthalen-2-yl]-acetic acid methyl ester

HRID 238629Notes

Reaction equation

HRID 238629 reaction equation
[CH3:1][O:2][C:3](=[O:24])[CH2:4][C:5]1[CH:14]=[C:13](OS(C(F)(F)F)(=O)=O)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:23])[CH:11]=2)[CH:6]=1.[CH3:25][S:26]([C:29]1[CH:34]=[CH:33][C:32]([NH2:35])=[CH:31][CH:30]=1)(=[O:28])=[O:27].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.O.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:24])[CH2:4][C:5]1[CH:14]=[C:13]([NH:35][C:32]2[CH:31]=[CH:30][C:29]([S:26]([CH3:25])(=[O:28])=[O:27])=[CH:34][CH:33]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:23])[CH:11]=2)[CH:6]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 796174-(Methylsulfonyl)anilineHCID 634876Binap, (A+-)-HCID 59326501(6-Fluoro-4-trifluoromethanesulfonyloxy-naphthalen-2-yl)-acetic acid methyl ester

Product 1

HCID 59326607[6-Fluoro-4-(4-methanesulfonyl-phenylamino)-naphthalen-2-yl]-acetic acid methyl esterYield 69.9%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
160 °C

Procedure

To a solution of (6-fluoro-4-trifluoromethanesulfonyloxy-naphthalen-2-yl)-acetic acid methyl ester (115 mg, 0.31 mmol) and 4-methanesulfonyl-phenylamine (59 mg, 0.35 mmol) in N,N-dimethylformamide (3 mL), was added (R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (39 mg, 0.063 mmol), tris(dibenzylideneacetone)dipalladium(0) (14 mg, 0.016 mmol), and cesium carbonate (102 mg, 0.31 mmol). After being heated under microwave conditions (160° C., 15 minutes), the resulting mixture was diluted with water (10 mL) and extracted with ethyl acetate (15 mL×3). The organic layer was washed with brine, then dried over sodium sulfate, and concentrated in vacuo. The residue was purified by column chromatography (gradient elution with 0-50% ethyl acetate in hexanes) to afford [6-fluoro-4-(4-methanesulfonyl-phenylamino)-naphthalen-2-yl]-acetic acid methyl ester (84.0 mg, 69% yield) as a yellow solid.

Workup

  1. extractionextracted with ethyl acetate (15 mL×3)
  2. washThe organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography (gradient elution with 0-50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-a697854d426a40d7b02b7ed418c24dfa
Source dataset
uspto-grants-2014_02
Patent number
US08642629B2

Reaction notes

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