تفاعل #657337

معادلة التفاعل

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

dimethylformamide

phosphorus(V) oxychloride

→

title compound

المردود 67.0%

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

المردود 67.0%

المذيبات

chloroform

chloroform

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةthe reaction vessel was warmed to 23° C. for 10 min
2. 2
   درجة الحرارةthen re-cooled to 0° C
3. 3
   workup.STIRRINGAfter stirring a further 5 min at 0° C. the reaction
4. 4
   درجة الحرارةwas warmed
5. 5
   درجة الحرارةto reflux (oil bath) for 4 h
6. 6
   درجة الحرارةthen cooled to 23° C.
7. 7
   أخرىpartitioned between dichloromethane and water (100 mL each)
8. 8
   أخرىthe organic layer was separated
9. 9
   غسيلThe organic layer was washed with brine (100 mL)
10. 10
    استخلاصThe original aqueous layer was re-extracted with dichloromethane (100 mL)
11. 11
    تجفيفdried (MgSO4)
12. 12
    ترشيحfiltered
13. 13
    تركيزconcentrated
14. 14
    أخرىThe product was purified
15. 15
    غسيلthen eluted with ethyl acetate in heptane (0-40% ethyl acetate linear gradient over 16 column volumes at a flow rate of 60 mL/min)

الإجراء التجريبي

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.

المصدر