Potassium Carbonate → HCID 86657982, compound

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).

1. temperaturecooling
2. custompartitioned
3. dry with materialThe organic layer was dried over sodium sulfate
4. customThe solution after removal
5. additionof desiccant was added to the dimethylformamide reaction mixture above, and the mixture
6. stirringwas stirred at room temperature overnight
7. additionTo the reaction mixture was added water (500 mL)
8. stirringthe mixture was stirred
9. extractionextracted twice with ethyl acetate (500 mL)
10. washThe extract was washed successively with saturated aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride solution (each 500 mL), and
11. dry with materialdried over anhydrous sodium sulfate
12. customThe desiccant was removed
13. customthe solvent was evaporated
14. customthe obtained residue was purified by column chromatography (
15. washYamazen HI-FLASH™ COLUMN size 3 L, elution solvent

ORD record

ord-4dfe5d22e90c46ed8b11c7ae221f866a

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08497382B2