تفاعل #992743

معادلة التفاعل

4-bromo-3-chloro-6-fluoro-quinoline

NaH

diethyl malonate

NaHSO4

→

title compound

المردود 113.3%

2-(6-fluoro-quinolin-4-yl)-malonic acid diethyl ester

المردود 113.3%

المذيبات

dioxane

1,4-dioxane

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةheated at 80° C. for 1 h
2. 2
   درجة الحرارةAfter cooling to rt
3. 3
   workup.STIRRINGThe mixture was stirred at 100° C. overnight
4. 4
   درجة الحرارةAfter cooling
5. 5
   workup.STIRRINGThe mixture was stirred 30 min
6. 6
   أخرىThe two layers were decanted
7. 7
   استخلاصthe aq. layer was extracted three times with EA (3×150 mL)
8. 8
   غسيلlayers were washed with brine
9. 9
   تجفيفdried over Na2SO4
10. 10
    ترشيحfiltered
11. 11
    تركيزconcentrated to dryness
12. 12
    أخرىThe residue was triturated in DCM

الإجراء التجريبي

To a suspension of NaH (60% in oil dispersion, 2.2 g, 54 mmol) in 1,4-dioxane (26 mL) was added diethyl malonate (9 mL, 59 mmol). The reaction mixture was stirred at rt for 5 min and heated at 80° C. for 1 h. After cooling to rt, CuBr (1.0 g) and 4-bromo-3-chloro-6-fluoro-quinoline (5 g, 19.4 mmol) in dioxane (8 mL) were successively added. The mixture was stirred at 100° C. overnight. After cooling, 10% aq. NaHSO4 (100 mL) was added. The mixture was stirred 30 min. The two layers were decanted and the aq. layer was extracted three times with EA (3×150 mL). The combined org. layers were washed with brine, dried over Na2SO4, filtered and concentrated to dryness. The residue was triturated in DCM to yield the title compound as a yellow solid (6.71 g, 100% yield).

المصدر