5-Thiazolecarboxylic acid, 4-methyl-, ethyl ester → 5-Thiazolecarboxylic acid, 2-(3-cyano-4-(2-methylpropoxy)phenyl)-4-methyl-, ethyl ester

Participants

Reaction Conditions

Reaction Steps

To a test tube-type reaction vessel (60 mL) were added ethyl 4-methylthiazole-5-carboxylate (2.14 g, 12.5 mmol), 5-bromo-2-isobutoxybenzonitrile (2.54 g, 10.0 mmol) obtained in the Reference Example 1, and a solvent (7.6 mL), a palladium compound (0.025 mmol), a ligand (0.10 mmol), a base (21.0 mmol), carboxylic acid (0.10 mmol), an additive (0.10 mmol), and a reducing agent (0.10 mmol) listed in the Table 10. Thereafter, the reaction vessel was filled with nitrogen gas and sealed air-tight and the mixed solution was heated to 140° C. and stirred for 24 hours. After the completion of the reaction, a portion of the reaction solution was diluted with xylene and DMSO and the resulting solution was analyzed by HPLC measurement. The total HPLC area % of the compound A to D and TM was adjusted to 100%, the calculated yield of the subject material was computed from each HPLC area %. Calculation of the calculated yield from the HPLC area % of subject material was carried out by applying corresponding numbers in the following calculation formula. Yield (%) of TM=total amount of TM (mol)/[{total amount of A (mol)+total amount of C (mol)×2+total amount of TM (mol)}]×100 Total amount of each compound (mol)=HPLC area value (mAU) of each compound/HPLC area value (mAU/mol) per mol of each compound

Provenance & Evidence