反应详情

温度

0 °C

Oxalyl chloride (106 mL, 1.22 mol) is added over 1 hour to dimethylformamide (92 mL) in methylene chloride (1250 mL) at 0° C. To this is added a solution of 2(R)-[[4-methoxybenzenesulfonyl](3-picolyl)amino]-3-methylbutanoic acid hydrochloride (248 g, 0.6 mol) in dimethylformamide (450 mL) over 1 hour, maintaining the temperature at 0° C. This solution is stirred an additional 2 hours at room temperature, and then added dropwise to a mixture of hydroxylamine (460 g of a 50% aqueous solution, 6.82 mol) in tetrahydrofuran (2400 mL). The reaction is stirred an additional 3 hours at 5° C., and then at room temperature overnight. The reaction mixture is filtered, the organic layer is collected, and the solvent is evaporated. The crude product is re-dissolved in methylene chloride (2 L), washed with water (2×1 L), saturated sodium bicarbonate (4×1 L), brine (1 L), dried (Na2SO4), and the solvent is evaporated. The product is dissolved in ethyl acetate (700 mL) and diluted with ether (1400 mL) to induce precipitation. The pure product is collected by filtration to provide N-hydroxy-2(R)-[[4-methoxybenzenesulfonyl](3-picolyl)amino]-3-methylbutanamide. After conversion to the hydrochloride salt, a white solid is obtained, m.p. 169°-170° C. (dec).

1. stirringThe reaction is stirred an additional 3 hours at 5° C.
2. customat room temperature
3. customovernight
4. filtrationThe reaction mixture is filtered
5. customthe organic layer is collected
6. customthe solvent is evaporated
7. dissolutionThe crude product is re-dissolved in methylene chloride (2 L)
8. washwashed with water (2×1 L), saturated sodium bicarbonate (4×1 L), brine (1 L)
9. dry with materialdried (Na2SO4)
10. customthe solvent is evaporated
11. dissolutionThe product is dissolved in ethyl acetate (700 mL)
12. additiondiluted with ether (1400 mL)
13. customprecipitation
14. filtrationThe pure product is collected by filtration