반응 #657336

반응 방정식

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

benzoxazinone

aniline

→

title compound

수율 85.0%

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

수율 85.0%

용매

ethyl acetate

반응 조건

후처리

1. 1
   여과The mixture was filtered through a pad of Celite
2. 2
   세척washing with ethyl acetate (100 mL)
3. 3
   농축The solution was concentrated
4. 4
   workup.DISSOLUTIONre-dissolved in ethyl acetate (100 mL)
5. 5
   온도refluxed for 2 h
6. 6
   workup.ADDITIONPara-toluenesulfonic acid hydrate (111 mg) was added
7. 7
   기타resulting solution
8. 8
   온도was refluxed for a further 1 h
9. 9
   온도The solution was cooled to 23° C.
10. 10
    세척then washed successively with water, 1.0 N aqueous hydrochloric acid, saturated aqueous brine (100 mL each)
11. 11
    건조dried (MgSO4)
12. 12
    여과filtered
13. 13
    농축concentrated
14. 14
    기타The product was purified
15. 15
    세척then eluted with methanol in dichloromethane (0-5% methanol linear gradient over 18 column volumes at a flow rate of 60 mL/min)

실험 절차

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.

출처