تفاعل #45877

معادلة التفاعل

2-Amino-5-bromo-4-fluoro-3-hydroxy-6-methylbenzonitrile

3-chlorophenylboronic acid

cesium carbonate

→

compound

المردود 78.0%

4-Amino-3′-chloro-6-fluoro-5-hydroxy-3-methylbiphenyl-3-carbonitrile

المردود 78.0%

المذيبات

1,4-dioxane

water

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةAfter cooling to room temperature
2. 2
   أخرىthe insoluble matter was separated by filtration
3. 3
   غسيلwith washing with ethyl acetate
4. 4
   تركيزThe filtrate was concentrated under reduced pressure
5. 5
   أخرىThe aqueous layer was separated
6. 6
   استخلاصthis was further extracted twice with ethyl acetate
7. 7
   غسيلwashed with saturated brine
8. 8
   تجفيفdried over anhydrous sodium sulfate
9. 9
   أخرىThe insoluble matter was separated by filtration
10. 10
    أخرىthe solvent was evaporated away
11. 11
    أخرىthe resulting residue was purified by middle-pressure liquid chromatography (eluent, chloroform

الإجراء التجريبي

2-Amino-5-bromo-4-fluoro-3-hydroxy-6-methylbenzonitrile (I-75) (2.0 g, 8.16 mmol), 3-chlorophenylboronic acid (2.63 g, 16.3 mmol) and cesium carbonate (5.32 g, 16.3 mmol) were dissolved in 1,4-dioxane (90 ml)/water (10 ml), and at room temperature, (tetrakistriphenylphosphine)palladium(0) (943 mg, 0.82 mmol) was added. The solution was stirred in a nitrogen steam at 100° C. for 12 hours. After cooling to room temperature, the insoluble matter was separated by filtration with washing with ethyl acetate. The filtrate was concentrated under reduced pressure, and the residue was fractionated with ethyl acetate and saturated brine. The aqueous layer was separated, this was further extracted twice with ethyl acetate. The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, the solvent was evaporated away, and the resulting residue was purified by middle-pressure liquid chromatography (eluent, chloroform:ethyl acetate=95:5, v/v) to obtain the entitled compound (1.76 g, 78%) as a pale brown solid.

المصدر