Reaction #63734

Reaction equation

2,3-dimethyl-4-propoxypyridine 1-oxide

trichloroacetyl chloride

trichloroacetyl chloride

carbon dioxide

ether

→

2-chloromethyl-3-methyl-4-propoxypyridine hydrochloride

Solvents

isopropyl acetate

isopropyl acetate

Conditions

Workup

1. 1
   Temperatureat reflux temperature (oil-bath 130° )
2. 2
   Temperaturecooled to 10° with ice
3. 3
   workup.STIRRINGstirred for 1 hour
4. 4
   Temperaturewhile cooling with ice
5. 5
   OtherThe crystalline precipitate which separates during the entire reaction
6. 6
   Filtrationis filtered off under suction
7. 7
   Washwashed with ice-cold isopropyl acetate and ether
8. 8
   OtherCrystalline reaction product can again be obtained from the mother liquor

Procedure

A solution of 23 ml of trichloroacetyl chloride in 50 ml of isopropyl acetate is added dropwise during 1 hour to a solution, boiling at reflux under argon, of 13 g of 2,3-dimethyl-4-propoxypyridine 1-oxide in 250 ml of isopropyl acetate. At the beginning the reaction exhibits a very exothermic character. During the addition of the first mol equivalent of trichloroacetyl chloride a vigorous evolution of carbon dioxide is observed. The solution is subsequently stirred under argon for a further 15 minutes at reflux temperature (oil-bath 130° ), cooled to 10° with ice. treated with 100 ml of ether and stirred for 1 hour while cooling with ice. The crystalline precipitate which separates during the entire reaction is filtered off under suction and washed with ice-cold isopropyl acetate and ether. Crystalline reaction product can again be obtained from the mother liquor. The 2-chloromethyl-3-methyl-4-propoxypyridine hydrochloride obtained is processed directly.

Source