Sodium Hydroxide → 4-{5-[4-(5-Isopropyl-2-Methyl-1,3-Thiazol-4-Yl)-Phenoxy]-Pentoxy}-Benzonitrile

Participants

Reaction Steps

While 72.6 g of 4-(5-isopropyl-2-methyl-1,3-thiazol-4-yl)-phenol (6) prepared in Example 4 were added to 850 ml of dimethylformamide and stirred, 15.0 g of sodium hydroxide were added. The reaction temperature was gradually increased and stirring was continued at 50-55° C. for 30 min. Thereafter, 70.0 g of 4-(5-chloro-pentoxy)-benzonitrile (8), prepared in Example 5, or 95.3 g of 4-(5-iodo-pentoxy)-benzonitrile (9), prepared in Example 6, were added. The reaction temperature was gradually increased and stirring was continued at 80-90° C. for 3 hr. After the reaction was completed, the temperature was decreased to room temperature, and the resultant reaction mixture was added with 850 ml of ethylacetate, and then washed with water and brine. Subsequently, the ethylacetate layer was dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residual solution was crystallized with ethylacetate and n-hexane, thus obtaining 114 g (yield: 90%) of a title compound as a light yellow solid through the reaction with the compound (8), or 119.6 g (yield: 94%) of a title compound as a light yellow solid through the reaction with the compound (9).

Provenance & Evidence