反应详情

温度

0 °C

N-(2,4-dimethoxybenzyl)-1,3-thiazol-2-amine (Preparation 6, 2.34 g, 9.35 mmol, 0.95 eq) was suspended in THF (20 ml) and stirred at 0° C. for 10 minutes. 1,1,1,3,3,3-Hexanemethyldisilazane lithium salt (LiHMDS, 1M in THF, 19.5 ml, 20 mmol, 2.0 eq) was added dropwise maintaining the temperature below 30° C. and the reaction mixture stirred for a further 30 minutes. A solution of 4-(chlorosulfonyl)-3-fluorobenzoic acid (Preparation 9, 2.35 g, 9.85 mmol, 1 eq) in THF (15 ml) was added dropwise maintaining the reaction temperature below 30° C. and the reaction mixture stirred at room temperature for 2 hours. The reaction mixture was diluted with brine (10 ml), extracted into ethyl acetate (10 ml), dried over sodium sulphate, filtered and evaporated in vacuo. The crude material was slurried in t-butylmethyl ether and stirred at room temperature for 72 hours. The resulting solid was collected by filtration to yield the title compound as a beige solid (744 mg, 1.64 mmol, 17%).

1. temperaturemaintaining the temperature below 30° C.
2. stirringthe reaction mixture stirred for a further 30 minutes
3. temperaturemaintaining the reaction temperature below 30° C.
4. stirringthe reaction mixture stirred at room temperature for 2 hours
5. extractionextracted into ethyl acetate (10 ml)
6. dry with materialdried over sodium sulphate
7. filtrationfiltered
8. customevaporated in vacuo
9. stirringstirred at room temperature for 72 hours
10. filtrationThe resulting solid was collected by filtration