反应详情

温度

20 °C

Magnesium turnings (12.16 g) were charged into a round bottom flask. Tetrahydrofuran (50 mL) was added to the flask. A solution of ethyl bromide (50.2 g in 200 mL tetrahydrofuran) was prepared and 20 mL of this solution was slowly charged to the round bottom flask. Iodine (30 mg) was added. The reaction mixture was stirred at 20° C. to 22° C. for 10 minutes and the remaining amount of ethyl bromide was added slowly over 30 minutes. The reaction mixture was heated to gentle reflux for 30 minutes and cooled to 0° C. to −10° C. 2-Chloro-6-methylaniline (72.4 g) was added drop-wise at 0° C. and the temperature of the reaction mixture was slowly raised to 20° C. Ethyl 2-amino-1,3-thiazole-5-carboxylate (20 g) dissolved in tetrahydrofuran (200 mL) was slowly added to the reaction mixture over 60 minutes. The reaction mixture was stirred for 3 hours. The progress of the reaction was monitored by thin layer chromatography. The reaction mixture was further stirred for 16 hours and then poured slowly into 25% ammonium chloride solution (200 mL) with stirring. The oily layer was separated, diluted with ethyl acetate (200 mL), and washed with 2 N hydrochloric acid (200 mL). The layers were separated and the pH of the aqueous layer was adjusted to between 8 and 9 with saturated sodium bicarbonate solution (300 ml) and extracted with ethyl acetate (2×100 mL). The oily layer was collected, concentrated, and further purified by column chromatography to obtain the title compound.

1. temperatureThe reaction mixture was heated
2. temperatureto gentle reflux for 30 minutes
3. temperaturecooled to 0° C. to −10° C
4. additionwas slowly added to the reaction mixture over 60 minutes
5. stirringThe reaction mixture was stirred for 3 hours
6. stirringThe reaction mixture was further stirred for 16 hours
7. stirringwith stirring
8. customThe oily layer was separated
9. additiondiluted with ethyl acetate (200 mL)
10. washwashed with 2 N hydrochloric acid (200 mL)
11. customThe layers were separated
12. extractionextracted with ethyl acetate (2×100 mL)
13. customThe oily layer was collected
14. concentrationconcentrated
15. customfurther purified by column chromatography