تفاعل #77512
ord-46607720657741838a05f1c19a0b2ef9
معادلة التفاعل
المذيبات
ظروف التفاعل
المعالجة
- 1ترشيحThe mixture is filtered
- 2أخرىthe DMF is partially evaporated on a RE
- 3workup.DISSOLUTIONThe residue is dissolved with EtOAc and water
- 4أخرىthe water phase separated
- 5استخلاصextracted twice with EtOAc
- 6غسيلThe organic phases are washed with water
- 7استخلاصextracted with 200 ml of 1N HCl and 2 portions of 200 ml 0.5 N HCl
- 8غسيلwashed with saturated Na2CO3 solution and brine
- 9تجفيفdried (Na2SO4)
- 10تركيزconcentrated by evaporation
- 11أخرىColumn chromatography (SiO2, hexane/EtOAc 1:1→1:2) and recrystallisation from acetonitrile
الإجراء التجريبي
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).