2-(3-formyl-4-isobutoxyphenyl)-N,N,4-trimethylthiazole- 5-carboxamide synthesis

Yield:1380049-42-2 93.1%

Reaction Conditions:

with tetrabutylammomium bromide;potassium carbonate;potassium iodide in tetrahydrofuran;N,N-dimethyl-formamide at 25 - 65;Product distribution / selectivity;

Steps:

3

Example 4: Preparation of 2-[3-formyl-4-(2-methylpropoxy)phenyl]-N,N-4- trimethylthiazole-5-carboxamide:Charged 2-(3-formyl-4-hydroxyphenyl)-N,N-4-trimethylthiazole-5-carboxamide (20.0 gm) and dimethylformamide (100 ml) at 25°-30°C and stirred for 15 minutes. Charged potassium carbonate (38.0 gm), tetrabutylammonium bromide (2.3 gm) and potassium iodide (4.5 gm) to the reaction mixture, stirred and raised the temperature of reaction mixture to 55°-60°C. Added l-bromo-2-methylpropane solution in tetrahydrofuran (19 gm in 19 ml) maintaining temperature at 55°-60°C. Further maintain the reaction mixture at 62°-65°C for 6-8 hours. Monitored the reaction on TLC for complete conversion of starting material. Concentrated the reaction mixture under reduced pressure maintaining temperature below 40°C till one to two volume of solvent remained in the reaction. Cooled the reaction mixture to 25°-30°C and diluted the residual mixture with water (50 ml) and ethyl acetate (50ml). Extracted the aqueous layer with ethyl acetate (2x50 ml). Combined ethyl acetate layers, washed with saturated sodium chloride solution (50 ml), dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to get the solid product of 2-[3-formyl-4-(2-methylpropoxy)phenyl]-N,N-4-trimethylthiazole-5- carboxamide.Yield = 22.2 gm% yield = 93.1

References:

WO2012/73259,2012,A1 Location in patent:Page/Page column 21-22