反応 #657348

反応方程式

toluene

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

4-chlorophenylmagnesium bromide

→

title compound

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

溶媒

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
3. 3
   抽出The aqueous layer was extracted with EtOAc (3×)
4. 4
   洗浄the combined organics were washed with brine
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 EtOH (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 under reduced pressure
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×)
15. 15
    洗浄the combined organics were washed with brine
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 Intermediate 8) (40.0 g, 0.21 mol) in a toluene (560 mL)/ether (200 mL) mixture at 0° C. was added dropwise a solution of 4-chlorophenylmagnesium bromide (170 mL, 1M in Et2O, 0.17 mol). The reaction mixture was allowed to warm to RT and stirred for 1 h before being quenched with 1N HCl. The aqueous layer was extracted with EtOAc (3×) and the combined organics were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude compound was then dissolved in EtOH (400 mL) and 6N HCl (160 mL) was added. The reaction mixture was refluxed for 2 h before being concentrated under reduced pressure. The resulting solid was filtered and washed twice with ether before being suspended in EtOAc and neutralised with 1N NaOH. The aqueous layer was extracted with EtOAc (3×) and the combined organics were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The title compound was obtained as a yellow solid (39 g, 88% yield) which was used without further purification.

出典