反応 #657336

反応方程式

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

benzoxazinone

aniline

→

title compound

収率 85.0%

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

収率 85.0%

溶媒

ethyl acetate

反応条件

後処理

1. 1
   ろ過The mixture was filtered through a pad of Celite
2. 2
   洗浄washing with ethyl acetate (100 mL)
3. 3
   濃縮The solution was concentrated
4. 4
   workup.DISSOLUTIONre-dissolved in ethyl acetate (100 mL)
5. 5
   温度refluxed for 2 h
6. 6
   workup.ADDITIONPara-toluenesulfonic acid hydrate (111 mg) was added
7. 7
   その他resulting solution
8. 8
   温度was refluxed for a further 1 h
9. 9
   温度The solution was cooled to 23° C.
10. 10
    洗浄then washed successively with water, 1.0 N aqueous hydrochloric acid, saturated aqueous brine (100 mL each)
11. 11
    乾燥dried (MgSO4)
12. 12
    ろ過filtered
13. 13
    濃縮concentrated
14. 14
    その他The product was purified
15. 15
    洗浄then eluted with methanol in dichloromethane (0-5% methanol linear gradient over 18 column volumes at a flow rate of 60 mL/min)

実験手順

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.

出典