Reaction #1321

Reaction equation

6-iodonicotinic acid

ethanol

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride

→

title compound

Ethyl 6-iodonicotinoate

Solvents

dichloromethane

dichloromethane

Conditions

Workup

1. 1
   Concentrationconcentrated in vacuo
2. 2
   Otherpartitioned between 200 ml of water and 250 ml of ethyl ether
3. 3
   Otherthe layers were separated
4. 4
   WashThe aqueous phase was washed with 2×150 ml-portions of ethyl ether
5. 5
   Washwashed once with 75 ml of brine solution
6. 6
   Dryingdried over MgSO4
7. 7
   Filtrationfiltered
8. 8
   Concentrationconcentrated in vacuo to a yellow solid
9. 9
   OtherPurification by flash chromatography (silica, 10% ethyl acetate in hexane)

Procedure

To a suspension of 23.38 g (94.2 mmol) of 6-iodonicotinic acid in 100 ml of dichloromethane was added a solution of 19.86 g (103.6 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in 250 ml of dichloromethane. To this suspension was added 12.40 g (15.8 ml, 269.3 mmol) of ethanol (95%) and 1.15 g (9.4 mmol) of 4-dimethylaminopyridine. The resulting solution mixture was then heated at 50° C. in an oil bath for 24.5 hours, concentrated in vacuo, partitioned between 200 ml of water and 250 ml of ethyl ether, and the layers were separated. The aqueous phase was washed with 2×150 ml-portions of ethyl ether. All organic phases were combined, washed once with 75 ml of brine solution, dried over MgSO4, filtered and concentrated in vacuo to a yellow solid. Purification by flash chromatography (silica, 10% ethyl acetate in hexane) yielded the title compound as a white solid.

Source