反应 #657351

反应方程式

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

溶剂

toluene ether

反应条件

后处理

1. 1
   其他at 0° C.
2. 2
   其他before being quenched with 1N HCl (200 mL)
3. 3
   萃取The aqueous layer was extracted with EtOAc (3×150 mL)
4. 4
   洗涤the combined organics were washed with brine (100 mL)
5. 5
   干燥dried over Na2SO4
6. 6
   过滤filtered
7. 7
   浓缩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
    浓缩before being concentrated to one-third in volume
12. 12
    过滤The resulting solid was filtered
13. 13
    洗涤washed twice with ether
14. 14
    萃取The aqueous layer was extracted with EtOAc (3×150 mL)
15. 15
    洗涤the combined organics were washed with brine (150 mL)
16. 16
    干燥dried over Na2SO4
17. 17
    过滤filtered
18. 18
    浓缩concentrated under reduced pressure

实验过程

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 Et2O, 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 EtOH (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 NaOH. 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 A): m/z 262 [M+H]+, Rt 2.57 min.

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