Dimethyl Sulfide → 3-Bromo-6-chloro-2,4-dimethylpyridine 1-oxide

Temperature

0 °C

A suspension of urea hydrogen peroxide (33.9 g, 360 mmol) in CH2Cl2 (1.985 L) was cooled to 0° C. Trifluoracetic anhydride (25.4 mL, 180 mmol) was added and the reaction was warmed to r.t. and stirred for 10 minutes. Next, 3-bromo-6-chloro-2,4-dimethylpyridine (39.7 g, 180 mmol) was added as a solution in CH2Cl2 (198 mL). The reaction was stirred for 2.5 hours at room temperature and then dimethyl sulfide (170 mL, 2305 mmol) was added and stirring was continued for an additional 30 minutes. Next, water (2 L) was added, and the mixture was stirred for 10 minutes. The layers were separated and the aqueous layer was extracted with CH2Cl2 (3×500 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel with 0 to 75% EtOAc/heptanes afforded 3-bromo-6-chloro-2,4-dimethylpyridine 1-oxide. LCMS=235.9 and 237.9 (M+H)+ 1H NMR (CDCl3, 500 MHz) δ 7.29 (s, 1H), 2.79 (s, 3H), 2.40 (s, 3H).

1. temperaturethe reaction was warmed to r.t.
2. stirringThe reaction was stirred for 2.5 hours at room temperature
3. stirringstirring
4. waitwas continued for an additional 30 minutes
5. stirringthe mixture was stirred for 10 minutes
6. customThe layers were separated
7. extractionthe aqueous layer was extracted with CH2Cl2 (3×500 mL)
8. dry with materialThe combined organic layers were dried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated
11. customPurification of the residue by flash chromatography on silica gel with 0 to 75% EtOAc/heptanes

ORD record

ord-aaef0d50ebb945aaa83eeeb1e168fee8

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09221834B2