反応 #657337

反応方程式

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

dimethylformamide

phosphorus(V) oxychloride

→

title compound

収率 67.0%

{3-Chloro-6-[2-(3-fluoro-phenyl)-ethyl]-benzo[1,4]oxazin-2-ylidenemethyl}-dimethyl-amine

収率 67.0%

溶媒

chloroform

chloroform

反応条件

後処理

1. 1
   温度the reaction vessel was warmed to 23° C. for 10 min
2. 2
   温度then re-cooled to 0° C
3. 3
   workup.STIRRINGAfter stirring a further 5 min at 0° C. the reaction
4. 4
   温度was warmed
5. 5
   温度to reflux (oil bath) for 4 h
6. 6
   温度then cooled to 23° C.
7. 7
   その他partitioned between dichloromethane and water (100 mL each)
8. 8
   その他the organic layer was separated
9. 9
   洗浄The organic layer was washed with brine (100 mL)
10. 10
    抽出The original aqueous layer was re-extracted with dichloromethane (100 mL)
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 ethyl acetate in heptane (0-40% ethyl acetate linear gradient over 16 column volumes at a flow rate of 60 mL/min)

実験手順

To a solution of dimethylformamide (0.82 mL, 10.6 mmol, 2.5 equiv) in chloroform (10 mL) at 0° C. was added phosphorus(V) oxychloride (0.78 mL, 8.49 mmol, 2 equiv). After stirring 10 min at 0° C., the reaction vessel was warmed to 23° C. for 10 min then re-cooled to 0° C. A solution of 6-[2-(3-fluoro-phenyl)-ethyl]-4H-benzo[1,4]oxazin-3-one in chloroform (7 mL) was added. After stirring a further 5 min at 0° C. the reaction was warmed to reflux (oil bath) for 4 h then cooled to 23° C. and partitioned between dichloromethane and water (100 mL each). The aqueous layer was adjusted to pH 12 with 5 N aqueous sodium hydroxide, and then the organic layer was separated. The organic layer was washed with brine (100 mL) and set aside. The original aqueous layer was re-extracted with dichloromethane (100 mL). The two organic extracts were combined, 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 ethyl acetate in heptane (0-40% ethyl acetate linear gradient over 16 column volumes at a flow rate of 60 mL/min) to give 985 mg (2.86 mmol, 67%) of the title compound as an orange/brown oil.

出典