تفاعل #159486

معادلة التفاعل

3-(5-bromo-2-ethyl-phenyl)-1,8,8-trimethylbicyclo[3.2.1]octane-2,4-dione

4-chlorophenylboronic acid

Cesium fluoride

→

3-(4′-chloro-4-ethylbiphen-3-yl)bicyclo[3.2.2]nonane-2,4-dione

المذيبات

dimethoxyethane

ظروف التفاعل

المعالجة

1. 1
   أخرىThe reaction mixture is then evacuated
2. 2
   أخرىflushed with nitrogen (degassing cycle repeated 4 times)
3. 3
   درجة الحرارةthe reaction mixture is heated at 80° C. for 5.5 hours
4. 4
   درجة الحرارةAfter cooling to room temperature the suspension
5. 5
   ترشيحis filtered through diatomaceous earth
6. 6
   غسيلwashed with 2M hydrochloric acid (5 ml) and dichloromethane (5 ml)
7. 7
   أخرىThe organic phase is separated
8. 8
   استخلاصthe aqueous phase is extracted with dichloromethane (5 ml×2)
9. 9
   تجفيفdried over magnesium sulfate
10. 10
    ترشيحfiltered
11. 11
    تركيزthe filtrate concentrated under reduced pressure
12. 12
    أخرىto give a brown gum
13. 13
    أخرىThe crude product is purified by flash column chromatography on silica gel (100% to 40% hexane/ethyl acetate eluant ratio)
14. 14
    أخرىfurther purified by preparative reverse-phase HPLC
15. 15
    أخرىto afford

الإجراء التجريبي

A solution of 3-(5-bromo-2-ethyl-phenyl)-1,8,8-trimethylbicyclo[3.2.1]octane-2,4-dione (0.035 g, 0.1 mmol) and 4-chlorophenylboronic acid (0.022 g, 0.14 mmol) in anhydrous dimethoxyethane (2 ml) is stirred at room temperature under an atmosphere of nitrogen. The reaction mixture is then evacuated and flushed with nitrogen (degassing cycle repeated 4 times). Cesium fluoride (0.046 g, 0.30 mmol) is added, and the suspension is stirred at room temperature for 1 hour. Next [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.012 g, 0.015 mmol) is added in one portion, and the reaction mixture is heated at 80° C. for 5.5 hours. After cooling to room temperature the suspension is filtered through diatomaceous earth, then washed with 2M hydrochloric acid (5 ml) and dichloromethane (5 ml). The organic phase is separated, and the aqueous phase is extracted with dichloromethane (5 ml×2). All organics are combined, dried over magnesium sulfate, filtered and the filtrate concentrated under reduced pressure to give a brown gum. The crude product is purified by flash column chromatography on silica gel (100% to 40% hexane/ethyl acetate eluant ratio), then further purified by preparative reverse-phase HPLC to afford to afford 3-(4′-chloro-4-ethylbiphen-3-yl)bicyclo[3.2.2]nonane-2,4-dione.

المصدر