Potassium Carbonate → HCID 86657982, compound

Participants

Reaction Steps

2-(1-tert-Butoxycarbonyl-1-methyl-ethylsulfanyl)-1,3-thiazole-4-carboxylic acid (30.34 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (19.17 g) and 1-hydroxybenzotriazole (13.35 g) were dissolved in dimethylformamide (550 ml) under ice-cooling, and the mixture was warmed to room temperature and stirred for 1 hr 30 min. Separately, N,O-dimethylhydroxylamine hydrochloride (14.63 g) was suspended in tetrahydrofuran (50 mL), 20% aqueous potassium carbonate solution (50 mL) was added to convert same to a free amine and partitioned. The organic layer was dried over sodium sulfate. The solution after removal of desiccant was added to the dimethylformamide reaction mixture above, and the mixture was stirred at room temperature overnight. To the reaction mixture was added water (500 mL) and the mixture was stirred, and extracted twice with ethyl acetate (500 mL). The extract was washed successively with saturated aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride solution (each 500 mL), and dried over anhydrous sodium sulfate. The desiccant was removed, the solvent was evaporated, and the obtained residue was purified by column chromatography (Yamazen HI-FLASH™ COLUMN size 3 L, elution solvent: hexane/ethyl acetate=4/1-5/5, performed twice) to give 2-[(4-{[methoxy(methyl)amino]carbonyl}-1,3-thiazol-2-yl)thio]-2-methylpropionic acid tert-butyl ester (32.56 g). 30.54 g of this compound was dissolved in tetrahydrofuran (400 mL), and methylmagnesium bromide (1.4 mol/L, toluene/tetrahydrofuran=75/25 solution) (68 mL) was added dropwise over 30 min under ice-cooling. After 1 hr 25 min, methyl magnesium bromide solution (5 mL) was added, and the mixture was stirred for 1 hr 10 min. The disappearance of the starting materials was confirmed by thin layer chromatography, 0.5 mol/L aqueous hydrochloric acid (200 mL) was added, the mixture was stirred and extracted with ethyl acetate (500 mL). The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution, and saturated aqueous sodium chloride solution (each 200 mL), and dried over anhydrous sodium sulfate. The solvent was evaporated and the obtained residue was purified by column chromatography (Yamazen HI-FLASH™ COLUMN size 3 L, elution solvent: hexane/ethyl acetate=95/5-50/50, performed 3 times) to give the title compound (21.89 g).

Provenance & Evidence