1,2-Dichloroethane → 1-Chloro-4-nitroisoquinoline

Temperature

102.5 °C

Stir a slurry of 1-hydroxy-4-nitroisoquinoline (62.2 g, 327 mmol) in POCl3 (180 mL) mechanically under nitrogen and heat to 100-105° C. for 1 hour resulting in a homogeneous dark brown solution. Exchange the condenser for a short-path distillation head, and remove excess POCl3 under reduced pressure (ca. 10-30 torr) resulting in a pot temperature of 55° C. To this mixture add 1,2-dichloroethane (150 mL), and warn the mixture to 70° C. to obtain a homogeneous solution. Cool the solution to 15° C., then add i-PrOH (450 mL) over 5 minutes resulting in an exotherm to 33° C. Stir the slurry for 3.5 hours at 15° C. then filter and wash with i-PrOH (3×100 mL). Air-dry the resulting solid overnight to afford 1-chloro-4-nitroisoquinoline (52.08, 76% yield) as a tan solid. (ES+): m/z 209/211 (M++H).

1. customresulting in a homogeneous dark brown solution
2. customExchange the condenser for a short-path distillation head, and remove excess POCl3 under reduced pressure (ca. 10-30 torr)
3. customresulting in a pot temperature of 55° C
4. customto 70° C.
5. customto obtain a homogeneous solution
6. temperatureCool the solution to 15° C.
7. filtrationthen filter
8. washwash with i-PrOH (3×100 mL)
9. customAir-dry the resulting solid overnight

ORD record

ord-4358f6d7b4bf4b50ab463c73e67445fe

Source dataset

uspto-grants-2009_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07582638B2