Reaktion #162594

Reaktionsgleichung

4-nitrophenylboronic acid pinacol ester

Na2CO3

3-(2,6-Dichloropyrimidin-4-yl)-8-oxa-3-aza-bicyclo[3.2.1]octane

3-(2,6-Dichloro-pyrimidin-4-yl)-8-oxa-3-aza-bicyclo[3.2.1]octane

→

3-[6-chloro-2-(4-nitro-phenyl)-pyrimidin-4-yl]-8-oxa-3-aza-bicyclo[3.2.1]octane

Ausbeute 10.0%

3-[2-chloro-6-(4-nitro-phenyl)-pyrimidin-4-yl]-8-oxa-3-aza-bicyclo[3.2.1]octane

Ausbeute 8.0%

Lösungsmittel

EtOH

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe mixture was degassed
2. 2
   Sonstigeby bubbling nitrogen through the solution
3. 3
   Temperaturthe mixture was heated
4. 4
   Temperaturunder reflux overnight
5. 5
   FiltrationThe mixture was filtered
6. 6
   Sonstigewere collected
7. 7
   Waschenwashed with water and dichloromethane
8. 8
   EinengenThe combined filtrates were concentrated
9. 9
   workup.DISSOLUTIONdissolved in dichloromethane
10. 10
    Waschenwashed with saturated NaHCO3
11. 11
    TrocknenThe organic phase was dried (MgSO4)
12. 12
    Filtrationfiltered
13. 13
    Einengenconcentrated
14. 14
    workup.ADDITIONThe crude product was added to a silica gel column
15. 15
    Waschenwas eluted with 10-50% ethyl acetate in hexanes
16. 16
    EinengenCollected fractions were concentrated

Vorschrift

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%).

Quelle