Reaction #77499

Reaction equation

water NH3

phosphorus oxychloride

HCl

4-[2-(6-methyl-pyridin-3-yl)-ethyl]-2H-isoquinolin-1-one

→

1-chloro-4-[2-(6-methyl-pyridin-3-yl)-ethyl]-isoquinoline

Solvents

EtOAc

dioxane

acetonitrile

Conditions

Workup

1. 1
   Otherthe water phase is separated
2. 2
   Extractionextraction
3. 3
   WashThe organic phases are washed with water and brine
4. 4
   Dryingdried (Na2SO4)
5. 5
   Concentrationconcentrated by evaporation

Procedure

3.12 g (11.8 mmol) of 4-[2-(6-methyl-pyridin-3-yl)-ethyl]-2H-isoquinolin-1-one in 48 ml of acetonitrile are mixed, whilst excluding air, with 3.7 ml (40 mmol) of phosphorus oxychloride and 6 ml of 4 N HCl in dioxane and stirred for 18 h at 55° C. After cooling to RT, water/NH3 conc. 10:1 (pH=9) and EtOAc are added, the water phase is separated and extraction effected twice with EtOAc. The organic phases are washed with water and brine, dried (Na2SO4) and concentrated by evaporation to form 1-chloro-4-[2-(6-methyl-pyridin-3-yl)-ethyl]-isoquinoline; 1H NMR (DMSO-d6) δ8.3 (m, 3H), 8.09 (s, 1H), 7.94 (t, 1H), 7.83 (t, 1H), 7.56 (d, 1H), 7.15 (d, 1H), 3.30 (t, H2C), 2.94 (t, H2C), 2.40 (s, H3C).

Source