反応 #169197

反応方程式

2-methyl-6-(methyloxy)-4H-3,1-benzoxazin-4-one

4-chlorophenylmagnesium bromide

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title compound

[2-amino-5-(methyloxy)phenyl](4-chlorophenyl)methanone

溶媒

toluene ether

反応条件

後処理

1. 1
   その他at 0° C.
2. 2
   その他before being quenched with 1N HCl (200 ml)
3. 3
   抽出The aqueous layer was extracted with EtOAc (3×150 ml)
4. 4
   洗浄the combined organics were washed with brine (100 ml)
5. 5
   乾燥dried over Na2SO4
6. 6
   ろ過filtered
7. 7
   濃縮concentrated under reduced pressure
8. 8
   workup.DISSOLUTIONThe crude compound was then dissolved in ethanol (400 ml)
9. 9
   workup.ADDITION6N HCl (160 ml) was added
10. 10
    温度The reaction mixture was refluxed for 2 h
11. 11
    濃縮before being concentrated to one-third in volume
12. 12
    ろ過The resulting solid was filtered
13. 13
    洗浄washed twice with ether
14. 14
    抽出The aqueous layer was extracted with EtOAc (3×150 ml)
15. 15
    洗浄the combined organics were washed with brine (150 ml)
16. 16
    乾燥dried over Na2SO4
17. 17
    ろ過filtered
18. 18
    濃縮concentrated under reduced pressure

実験手順

To a solution of 2-methyl-6-(methyloxy)-4H-3,1-benzoxazin-4-one (for a preparation see Reference compound A) (40.0 g, 0.21 mol) in a toluene/ether (2/1) mixture (760 ml) at 0° C. was added dropwise a solution of 4-chlorophenylmagnesium bromide (170 ml, 1M in diethyl ether, 0.17 mol). The reaction mixture was allowed to warm to room temperature and stirred for 1 h before being quenched with 1N HCl (200 ml). The aqueous layer was extracted with EtOAc (3×150 ml) and the combined organics were washed with brine (100 ml), dried over Na2SO4, filtered and concentrated under reduced pressure. The crude compound was then dissolved in ethanol (400 ml) and 6N HCl (160 ml) was added. The reaction mixture was refluxed for 2 h before being concentrated to one-third in volume. The resulting solid was filtered and washed twice with ether before being suspended in EtOAc and neutralised with 1N sodium hydroxide. The aqueous layer was extracted with EtOAc (3×150 ml) and the combined organics were washed with brine (150 ml), dried over Na2SO4, filtered and concentrated under reduced pressure. The title compound was obtained as a yellow solid (39 g, 88% yield); LC/MS (Method D): m/z 262 [M+H]+, Rt 2.57 min.

出典