Réaction #77512

Équation de réaction

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

Solvants

DMF

Conditions de réaction

Traitement

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

Mode opératoire

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).

Source