反应详情

温度

0 °C

A solution of 3-cyclopentyl-2-(4-methanesulfonyl-phenyl)-propionic acid (300 mg, 1.01 mmol) and dry N,N-dimethylformamide (2 drops) in methylene chloride (3 mL) was cooled to 0° C. and then treated dropwise with oxalyl chloride (115 μL, 1.32 mmol). The reaction mixture was stirred at 0° C. for 10 min and then stirred at 25° C. for 1 h. The reaction mixture was concentrated in vacuo. The resulting yellow oil was dissolved in a small amount of methylene chloride and then slowly added to a solution of 2-amino-5-chlorothiazole hydrochloride (259 mg, 1.52 mmol) and triethylamine (424 μL, 3.04 mmol) in N,N-dimethylformamide (3 mL). The resulting reaction mixture was then stirred at 25° C. for 15 h. The reaction mixture was then partitioned between water (50 mL) and ethyl acetate (50 mL), and the layers were separated. The aqueous layer was back-extracted with ethyl acetate (50 mL). The combined organic layers were then dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 1/1 hexanes/ethyl acetate) afforded the N-(5-chloro-thiazol-2-yl)-3-cyclopentyl-2-(4-methanesulfonyl-phenyl)-propionamide (106 mg, 25%) as a tan foam: mp 76-79° C. (foam to gel); EI-HRMS m/e calcd for C18H21ClN2O3S2 (M+) 412.0682, found 412.0683.

1. stirringstirred at 25° C. for 1 h
2. concentrationThe reaction mixture was concentrated in vacuo
3. dissolutionThe resulting yellow oil was dissolved in a small amount of methylene chloride
4. customThe resulting reaction mixture
5. stirringwas then stirred at 25° C. for 15 h
6. customThe reaction mixture was then partitioned between water (50 mL) and ethyl acetate (50 mL)
7. customthe layers were separated
8. extractionThe aqueous layer was back-extracted with ethyl acetate (50 mL)
9. dry with materialThe combined organic layers were then dried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo