Reaktion #49038

Reaktionsgleichung

3,4-Difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(3-oxo-isoxazolidin-2-ylmethyl)-benzamide

tetrabutylammonium fluoride

N,N-diisopropylethylamine

trimethylsilylacetylene

→

2-(4-ethynyl-2-fluoro-phenylamino)-3,4-difluoro-N-(2-hydroxy-ethoxy)-5-(3-oxo-isoxazolidin-2-ylmethyl)-benzamide

Ausbeute 37.0%

Lösungsmittel

methanol

methylene chloride

Reaktionsbedingungen

Aufarbeitung

1. 1
   Waschenwashed with saturated brine (2×15 ml)
2. 2
   TrocknenThe organic layer was dried over anhydrous magnesium sulfate
3. 3
   Einengenconcentrated under reduced pressure
4. 4
   workup.DISSOLUTIONThe resultant residue was dissolved in THF (2 ml)
5. 5
   workup.STIRRINGthe mixture was stirred for 1 hour
6. 6
   Einengenconcentrated under reduced pressure
7. 7
   SonstigeThe resultant residue was purified by preparative TLC (EtOAc/MeOH (8:1))

Vorschrift

3,4-Difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(3-oxo-isoxazolidin-2-ylmethyl)-benzamide (36.9 mg, 66.9 μmol) obtained in Example 37, bis(acetonitrile)dichloropalladium (II) (3.5 mg, 13.5 μmol), 3,3′,3″-phosphinidine-tris(benzenesulfonic acid) trisodium salt (19.0 mg, 33.4 μmol), and copper iodide (I) (2.6 mg, 13.6 μmol) were suspended in methanol (2.5 ml) under a nitrogen atmosphere. To this suspension, N,N-diisopropylethylamine (14.0 μl, 80.4 μmol) and trimethylsilylacetylene (47.3 μl, 334.7 μmol) were added at room temperature, and the mixture was stirred for 1 hour. The reaction mixture was diluted with methylene chloride (30 ml), and washed with saturated brine (2×15 ml). The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resultant residue was dissolved in THF (2 ml). To this solution, tetrabutylammonium fluoride (1.0 M solution in THF, 0.10 ml, 0.10 mmol) was added, and the mixture was stirred for 1 hour, and then concentrated under reduced pressure. The resultant residue was purified by preparative TLC (EtOAc/MeOH (8:1)) to give 2-(4-ethynyl-2-fluoro-phenylamino)-3,4-difluoro-N-(2-hydroxy-ethoxy)-5-(3-oxo-isoxazolidin-2-ylmethyl)-benzamide (Compound G-5, 11.1 mg, 37%) as a brown oil.

Quelle