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

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence