反应详情

3-(2,6-Dichloropyrimidin-4-yl)-8-oxa-3-aza-bicyclo[3.2.1]octane (9) was dissolved in toluene (24 mL) and EtOH (16 mL). To this solution was added 4-nitrophenylboronic acid pinacol ester (1.25 g, 5 mmol) and 8 mL of a 2M solution of Na2CO3. The mixture was degassed by bubbling nitrogen through the solution. Pd(PPh3)4 (231 mg, 0.2 mmol) was added and the mixture was heated under reflux overnight. The mixture was filtered. The solids, consisting of 3-[2,6-bis-(4-nitro-phenyl)-pyrimidin-4-yl]-8-oxa-3-aza-bicyclo[3.2.1]octane (15), were collected and washed with water and dichloromethane. The combined filtrates were concentrated, dissolved in dichloromethane and washed with saturated NaHCO3. The organic phase was dried (MgSO4), filtered and concentrated. The crude product was added to a silica gel column and was eluted with 10-50% ethyl acetate in hexanes. Collected fractions were concentrated to give 3-[6-chloro-2-(4-nitro-phenyl)-pyrimidin-4-yl]-8-oxa-3-aza-bicyclo[3.2.1]octane (13, 135 mg, 10%) along with 3-[2-chloro-6-(4-nitro-phenyl)-pyrimidin-4-yl]-8-oxa-3-aza-bicyclo[3.2.1]octane (14, 110 mg, 8%).

1. customThe mixture was degassed
2. customby bubbling nitrogen through the solution
3. temperaturethe mixture was heated
4. temperatureunder reflux overnight
5. filtrationThe mixture was filtered
6. customwere collected
7. washwashed with water and dichloromethane
8. concentrationThe combined filtrates were concentrated
9. dissolutiondissolved in dichloromethane
10. washwashed with saturated NaHCO3
11. dry with materialThe organic phase was dried (MgSO4)
12. filtrationfiltered
13. concentrationconcentrated
14. additionThe crude product was added to a silica gel column
15. washwas eluted with 10-50% ethyl acetate in hexanes
16. concentrationCollected fractions were concentrated