Reaktion #439538

Reaktionsgleichung

cis-1,2,6-trimethylpiperazine

2,2′-bis(diphenylphosphino)-1,1′-binaphthyl

cesium carbonate

D1

1-Acetyl-6-bromo-5-methoxyindoline

→

required product

Ausbeute 23.0%

cis-1-Acetyl-5-methoxy-6-(3,4,5-trimethylpiperazin-1-yl)indoline

Ausbeute 23.0%

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigein dry
2. 2
   Sonstigedegassed 1,4-dioxane (120 ml) under argon
3. 3
   Sonstigewas sonicated at 28° C. for 0.5 h
4. 4
   Sonstigeproducing a pink heterogeneous mixture
5. 5
   Temperaturheated
6. 6
   Temperaturat reflux for 70 h
7. 7
   Temperaturto cool
8. 8
   Filtrationfiltered
9. 9
   Einengenconcentrated under vacuum
10. 10
    workup.ADDITIONThe residue was treated with water
11. 11
    Extraktionextracted with EtOAc
12. 12
    ExtraktionThe organic solution was then extracted with 1M HCl acid
13. 13
    Extraktionthe aqueous extract
14. 14
    workup.ADDITIONwas basified by addition of K2CO3
15. 15
    Extraktionextracted with EtOAc
16. 16
    TrocknenThe extract was dried (Na2SO4)
17. 17
    Einengenconcentrated under vacuum
18. 18
    Sonstigeto leave an orange solid, which
19. 19
    Sonstigewas chromatographed on silica gel eluting with 0-10% MeOH/DCM

Vorschrift

A mixture of palladium (II) acetate (500 mg), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (2.0 g) and cesium carbonate (10.3 g) in dry degassed 1,4-dioxane (120 ml) under argon was sonicated at 28° C. for 0.5 h producing a pink heterogeneous mixture. This was treated with D1 (6.0 g, 22 mmole) followed by cis-1,2,6-trimethylpiperazine (J. Med. Chem. 1968, 11, 592; 4.8 g, 38 mmole) and heated with rapid stirring at reflux for 70 h. The mixture was allowed to cool, filtered, then concentrated under vacuum. The residue was treated with water and extracted with EtOAc. The organic solution was then extracted with 1M HCl acid and the aqueous extract was basified by addition of K2CO3 and extracted with EtOAc. The extract was dried (Na2SO4) and concentrated under vacuum to leave an orange solid, which was chromatographed on silica gel eluting with 0-10% MeOH/DCM to afford the required product as a pale yellow solid (1.6 g, 23%).

Quelle