Reaktion #77512

Reaktionsgleichung

rac. 2-iodo-benzoic acid-[1-methyl-3-(6-methoxy-pyridin-3-yl)-allylamide]

tributylamine

→

rac. 4-[1-(6-methoxy-pyridin-3-yl)-methylidene]-3-methyl-3,4-dihydro-2H-isoquinolin-1-one

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   FiltrationThe mixture is filtered
2. 2
   Sonstigethe DMF is partially evaporated on a RE
3. 3
   workup.DISSOLUTIONThe residue is dissolved with EtOAc and water
4. 4
   Sonstigethe water phase separated
5. 5
   Extraktionextracted twice with EtOAc
6. 6
   WaschenThe organic phases are washed with water
7. 7
   Extraktionextracted with 200 ml of 1N HCl and 2 portions of 200 ml 0.5 N HCl
8. 8
   Waschenwashed with saturated Na2CO3 solution and brine
9. 9
   Trocknendried (Na2SO4)
10. 10
    Einengenconcentrated by evaporation
11. 11
    SonstigeColumn chromatography (SiO2, hexane/EtOAc 1:1→1:2) and recrystallisation from acetonitrile

Vorschrift

Under a N2 atmosphere, 8 g (19 mmol) of an (E/Z) mixture of rac. 2-iodo-benzoic acid-[1-methyl-3-(6-methoxy-pyridin-3-yl)-allylamide], 5.9 g (19 mmol) of tetrabutylammonium chloride and 0.12 g of palladium diacetate are dissolved in 170 ml of DMF, then 8.9 g (48 mmol) of tributylamine are added and stirred for 20 h at 150° C. The mixture is filtered and the DMF is partially evaporated on a RE. The residue is dissolved with EtOAc and water, the water phase separated, extracted twice with EtOAc and discarded. The organic phases are washed with water, extracted with 200 ml of 1N HCl and 2 portions of 200 ml 0.5 N HCl, washed with saturated Na2CO3 solution and brine, dried (Na2SO4) and concentrated by evaporation. Column chromatography (SiO2, hexane/EtOAc 1:1→1:2) and recrystallisation from acetonitrile yield rac. 4-[1-(6-methoxy-pyridin-3-yl)-methylidene]-3-methyl-3,4-dihydro-2H-isoquinolin-1-one (m.p. 194-195° C.; FAB-MS: (M+H)+=281; TLC(hexane/EtOAc 1:1): Rf=0.26). The acidic aqueous extracts are collected in a solution of 60 g of K2CO3 in 0.5 l of water. Upon standing, 4-[(6-methoxy-pyridin-3-yl)-methyl]-3-methyl-2H-isoquinolin-1-one crystallises, and can be filtered off by suction, washed with water and recrystallised from boiling EtOAc/methanol (m.p. 234-236° C.; FAB-MS: (M+H)+=281; TLC(hexane/EtOAc 1:1): Rf=0.18).

Quelle