Reaction #77502

Reaction equation

water NH3

4-[2-(2-methoxy-pyridin-4-yl)-ethyl]-2H-isoquinolin-1-one

phosphorus oxychloride

HCl

→

1-chloro-4-[2-(2-methoxy-pyridin-4-yl)-ethyl]-isoquinoline

Solvents

EtOAc

acetonitrile

dioxane

Conditions

Workup

1. 1
   TemperatureAfter cooling to RT
2. 2
   Otherthe water phase is separated
3. 3
   Extractionextraction
4. 4
   WashThe organic phases are washed with water and brine
5. 5
   Dryingdried (Na2SO4)
6. 6
   Concentrationconcentrated by evaporation

Procedure

Under a N2 atmosphere, 160 mg (0.57 mmol) of 4-[2-(2-methoxy-pyridin-4-yl)-ethyl]-2H-isoquinolin-1-one in 3.7 ml of acetonitrile are mixed with 131 μl (1.43 mmol) of phosphorus oxychloride and 0.28 ml of 4 N HCl in dioxane and stirred for 7 h at 65° C. After cooling to RT, water/NH3 conc. 10:1 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-(2-methoxy-pyridin-4-yl)-ethyl]-isoquinoline; 1H NMR (DMSO-d6) δ8.30 (d, 1H), 8.27 (d, 1H), 8.13 (s, 1H), 8.03 (d, 1H), 7.94 (t, 1H), 7.85 (t, 1H), 6.90 (d, 1H), 6.73 (s, 1H), 3.80 (s, H3C), 3.32 (t, H2C), 2.95 (t, H2C).

Source