Reaktion #657336

Reaktionsgleichung

[4-(3-fluoro-phenylethynyl)-2-nitro-phenoxy]-acetic acid ethyl ester

benzoxazinone

aniline

→

title compound

Ausbeute 85.0%

6-[2-(3-Fluoro-phenyl)-ethyl]-4H-benzo[1,4]oxazin-3-one

Ausbeute 85.0%

Lösungsmittel

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   FiltrationThe mixture was filtered through a pad of Celite
2. 2
   Waschenwashing with ethyl acetate (100 mL)
3. 3
   EinengenThe solution was concentrated
4. 4
   workup.DISSOLUTIONre-dissolved in ethyl acetate (100 mL)
5. 5
   Temperaturrefluxed for 2 h
6. 6
   workup.ADDITIONPara-toluenesulfonic acid hydrate (111 mg) was added
7. 7
   Sonstigeresulting solution
8. 8
   Temperaturwas refluxed for a further 1 h
9. 9
   TemperaturThe solution was cooled to 23° C.
10. 10
    Waschenthen washed successively with water, 1.0 N aqueous hydrochloric acid, saturated aqueous brine (100 mL each)
11. 11
    Trocknendried (MgSO4)
12. 12
    Filtrationfiltered
13. 13
    Einengenconcentrated
14. 14
    SonstigeThe product was purified
15. 15
    Waschenthen eluted with methanol in dichloromethane (0-5% methanol linear gradient over 18 column volumes at a flow rate of 60 mL/min)

Vorschrift

To a solution of [4-(3-fluoro-phenylethynyl)-2-nitro-phenoxy]-acetic acid ethyl ester (1.72 g, 5.01 mmol, 1 equiv) in ethyl acetate (50 mL) was added palladium on carbon (500 mg, 10 wt. %, wet, Degussa type). The reaction vessel was placed under an atmosphere of hydrogen (balloon) and stirred at 23° C. for 15 h. At this time LCMS analysis indicated the reaction contains a mixture of the desired benzoxazinone product (major) and uncyclized aniline (minor). The mixture was filtered through a pad of Celite, washing with ethyl acetate (100 mL). The solution was concentrated, then re-dissolved in ethyl acetate (100 mL) and refluxed for 2 h. LCMS analysis indicates no improvement in cyclized:uncyclized ratio. Para-toluenesulfonic acid hydrate (111 mg) was added and resulting solution was refluxed for a further 1 h. The solution was cooled to 23° C. then washed successively with water, 1.0 N aqueous hydrochloric acid, saturated aqueous brine (100 mL each), dried (MgSO4), filtered and concentrated. The product was purified using an Isco CombiFlash automated chromatography system. The residue was loaded onto a 80 g silica gel column as a solution in dichloromethane (5 mL) then eluted with methanol in dichloromethane (0-5% methanol linear gradient over 18 column volumes at a flow rate of 60 mL/min) to give 1.15 g (4.24 mmol, 85%) of the title compound as a tan solid.

Quelle