Reaction #58729

Reaction equation

6-methyl nicotinic acid methyl ester

iodine

2-iodo-2-methylpropane

trifluoroacetic acid

NaHCO3

Na2S2O3

→

title compound

Yield 46.3%

6-Formyl-nicotinic acid methyl ester

Yield 46.3%

Solvents

DMSO

Conditions

Workup

1. 1
   ExtractionThe reaction mixture was extracted with ethyl acetate (3×100 mL)
2. 2
   DryingThe combined organic phases were dried over anhydrous Na2SO4
3. 3
   Filtrationfiltered
4. 4
   Concentrationconcentrated

Procedure

A solution of 6-methyl nicotinic acid methyl ester (1.00 g, 6.62 mmol), iodine (1.68 g, 6.62 mmol), 2-iodo-2-methylpropane (0.478.g, 2.60 mmol) and trifluoroacetic acid (2.26 g, 19.8 mmol) in anhydrous DMSO was heated for 3 h at 160° C. The reaction mixture was cooled to room temperature (rt) and treated with 1 N aq. Na2S2O3 (50 mL). The reaction mixture was adjusted to pH 10 with 1 N aq. NaHCO3. The reaction mixture was extracted with ethyl acetate (3×100 mL). The combined organic phases were dried over anhydrous Na2SO4, filtered, and concentrated. Chromatography of the residue (SiO2; 0-3% EtOH:DCM) gave the title compound as a solid (0.506 g, 46%).

Source