Citric Acid → N-(5-bromo-2-chloro-3-pyridinyl)methanesulfonamide

Temperature

0 °C

A solution of 5-bromo-2-chloropyridin-3-amine (1.0 g, 4.8 mmol) and diisopropylethylamine (1.85 mL, 10.6 mmol) in dichloromethane (25 mL) was cooled to 0° C., and then methanesulfonyl chloride (750 uL, 9.6 mmol) was added slowly. The reaction mixture was stirred at 0° C. for 15 min and was then warmed to rt. After stirring for 2 h, water was added, and then the biphasic mixture was partitioned. The organic phase was dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was then dissolved in dioxane (10 mL) and water (10 mL). Potassium carbonate (2.76 g, 20 mmol) was added, and the reaction mixture was stirred for 15 h at rt. Water was then added to the mixture which was subsequently acidified with aqueous citric acid (10%). The aqueous mixture was extracted twice with ethyl acetate. The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (gradient, 100% hexanes to 50% hexanes: 50% ethyl acetate) to provide

1. temperaturewas then warmed to rt
2. stirringAfter stirring for 2 h
3. customthe biphasic mixture was partitioned
4. dry with materialThe organic phase was dried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. dissolutionThe residue was then dissolved in dioxane (10 mL)
8. stirringthe reaction mixture was stirred for 15 h at rt
9. extractionThe aqueous mixture was extracted twice with ethyl acetate
10. dry with materialThe combined organic extracts were dried over magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customThe residue was purified by flash chromatography (gradient, 100% hexanes to 50% hexanes: 50% ethyl acetate)
14. customto provide

ORD record

ord-a4b5f3dab6834e19af589bfd7459b1e7

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08637499B2