Reaction #710598

Reaction equation

4-chloro-8-methoxy-quinoline-3-carboxylic acid ethyl ester

chloroform

sulfuryl chloride

chloroform

sulfuryl chloride

→

title compound 26

Yield 29.0%

4,5,7-Trichloro-8-methoxy-quinoline-3-carboxylic acid ethyl ester

Yield 29.0%

Conditions

Workup

1. 1
   Temperatureto cool to RT
2. 2
   workup.ADDITIONadded to ice-aqueous ammonia
3. 3
   ExtractionThe mixture was then extracted with dichloromethane (20 mL×3)
4. 4
   Concentrationconcentrated

Procedure

To a stirred solution of 4-chloro-8-methoxy-quinoline-3-carboxylic acid ethyl ester (1.00 g, 3.76 mmol) in chloroform (50 mL) was added, dropwise over 1 h, a solution of sulfuryl chloride (15 mL) in chloroform (15 mL) whilst maintaining the temperature at 25-30° C. The solution was then heated at 60-70° C. for 48 h. During this time, further sulfuryl chloride (2 mL) was added at regular intervals (2, 24 and 30 h). The solution was allowed to cool to RT and added to ice-aqueous ammonia, adjusting the pH to 8. The mixture was then extracted with dichloromethane (20 mL×3), the extracts combined and concentrated. Column chromatography (silica gel, dichloromethane/methanol (100:1)) gave the title compound 26 as a cream solid (0.36 g, 29%). 1H-NMR (CDCl3, 400 MHz): δ 9.04 (s, 1H), 7.78 (s, 1H), 4.51 (q, J=7.1, 2 H), 4.14 (s, 3H), 1.46 (t, J=7.1, 3 H).

Source