Sodium Hydroxide → N-(5-bromo-2-methylpyridin-3-yl)methanesulfonamide

温度

0 °C

A solution of 5-bromo-2-methylpyridin-3-amine (187 mg, 1.0 mmol) and diisopropylethylamine (523 uL, 3.0 mmol) in dichloromethane (5 mL) was cooled to 0° C., and then methanesulfonyl chloride (155 uL, 2.0 mmol) was added slowly. The reaction mixture was stirred at 0° C. for 8 min and was then warmed to rt. After stirring for 1 h, the volatile materials were removed in vacuo. The residue was then dissolved in methanol (2.5 mL) and aqueous sodium hydroxide (2 M, 1.5 mL, 3 mmol) was added. The reaction mixture was stirred for 1 h 40 min at rt. Water was then added to the mixture which was subsequently extracted twice with dichloromethane. The combined organic extracts were extracted with aqueous citric acid (10%). The organic phase was discarded, and the aqueous phase was basified to pH ˜7.5 with aqueous sodium hydroxide (1 M). The aqueous mixture was extracted three times with dichloromethane. The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (50% hexanes:50% ethyl acetate) to provide N-(5-bromo-2-methylpyridin-3-yl)methanesulfonamide (111 mg, 0.42 mmol, 42% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 9.58 (s, 1H), 8.44 (d, 1H), 7.87 (d, 1H), 3.10 (s, 3H), 2.47 (s, 3H); MS (EI) for C7H9BrN2O2S: 265, 267 (Br isotopes, MH+).

1. temperaturewas then warmed to rt
2. stirringAfter stirring for 1 h
3. customthe volatile materials were removed in vacuo
4. dissolutionThe residue was then dissolved in methanol (2.5 mL)
5. stirringThe reaction mixture was stirred for 1 h 40 min at rt
6. extractionwas subsequently extracted twice with dichloromethane
7. extractionThe combined organic extracts were extracted with aqueous citric acid (10%)
8. extractionThe aqueous mixture was extracted three times with dichloromethane
9. dry with materialThe combined organic extracts were dried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customThe residue was purified by flash chromatography (50% hexanes:50% ethyl acetate)

ORDレコード

ord-7bfb63cea1334efaab954cd4bd2d42ac

出典データセット

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08648066B2