反应详情

Sodium hydride (0.029 g, 0.86 mmol) was added in portions to a solution of cyclopropanemethanol (CAN 2516-33-8, 20 mL) and the reaction mixture was stirred for 30 min at room temperature. 6-Chloro-5-(1,1-dioxido-isothiazolidin-2-yl)-pyridine-2-carboxylic acid methyl ester (0.050 g, 0.17 mmol) was added and the mixture was heated to 100° C. overnight, quenched with water and concentrated under reduced pressure. The residue was dissolved in water, extracted with ethyl acetate (50 mL). The pH of the aqueous layer was adjusted to 2 by addition of 1 N hydrochloric acid and subsequently extracted with ethyl acetate (3×20 mL). The combined extracts were washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product. The crude product was purified by column chromatography (silica gel, 4 g, 33% ethyl acetate in petroleum ether) to yield the title compound (25 mg, 0.08 mmol, 46%) as yellow solid; MS (EI): m/e=313.1 [M+H]+.

1. temperaturethe mixture was heated to 100° C. overnight
2. customquenched with water
3. concentrationconcentrated under reduced pressure
4. dissolutionThe residue was dissolved in water
5. extractionextracted with ethyl acetate (50 mL)
6. additionThe pH of the aqueous layer was adjusted to 2 by addition of 1 N hydrochloric acid
7. extractionsubsequently extracted with ethyl acetate (3×20 mL)
8. washThe combined extracts were washed with water and brine
9. dry with materialdried over anhydrous sodium sulfate
10. concentrationconcentrated under reduced pressure
11. customto give the crude product
12. customThe crude product was purified by column chromatography (silica gel, 4 g, 33% ethyl acetate in petroleum ether)