反応 #77512

反応方程式

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

溶媒

DMF

反応条件

後処理

1. 1
   ろ過The mixture is filtered
2. 2
   その他the DMF is partially evaporated on a RE
3. 3
   workup.DISSOLUTIONThe residue is dissolved with EtOAc and water
4. 4
   その他the water phase separated
5. 5
   抽出extracted twice with EtOAc
6. 6
   洗浄The organic phases are washed with water
7. 7
   抽出extracted with 200 ml of 1N HCl and 2 portions of 200 ml 0.5 N HCl
8. 8
   洗浄washed with saturated Na2CO3 solution and brine
9. 9
   乾燥dried (Na2SO4)
10. 10
    濃縮concentrated by evaporation
11. 11
    その他Column chromatography (SiO2, hexane/EtOAc 1:1→1:2) and recrystallisation from acetonitrile

実験手順

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).

出典