Sulfuric Acid → 3,6-Dichloro-4-isopropylpyridazine

Temperature

55 °C

A solution of 3,6-dichloropyridazine (22.5 g, 0.15 mol) in acetonitrile (35 mL), tetramethylene sulfone (107 mL) and water (245 mL) at room temperature was treated with isobutyric acid (14 mL, 0.151 mol) followed by silver nitrate (13 g, 0.075 mol). The reaction mixture was heated to 55° C. A solution of concentrated sulfuric acid (24 mL) in water (75 mL) was added in one portion followed by the dropwise addition over 35 min of a solution of ammonium persulfate (51.5 g, 0.22 mol) in water (75 mL). The reaction mixture was heated to 70° C. for 20 min and then cooled to room temperature and stirred for 24 h. At this time, the reaction was cooled to 0° C. and 28-30% ammonium hydroxide (100 mL) was added slowly dropwise to bring the reaction to pH=8. The reaction was diluted with water (500 mL) and was filtered over celite and washed well with ethyl acetate (500 mL). The water layer and the organic layer were separated. The organic layer was saved. The aqueous layer was extracted with ethyl acetate (2×500 mL). The combined organics were washed with water (1×400 mL) and a saturated aqueous sodium chloride solution (1×400 mL), dried with magnesium sulfate, filtered and concentrated under vacuum. The resulting oil was purified by column chromatography using silica gel eluted with petroleum ether followed by 10% ethyl acetate in petroleum ether to afford 3,6-dichloro-4-isopropyl pyridazine (7) (19.26 g, 67%) as an oil; (+)-HRMS m/z calcd for C7H8Cl2N2 (M+) 190.0065, found 190.0059. Molecular Weight=191.0612; Exact Mass=190.0065

1. temperatureThe reaction mixture was heated to 70° C. for 20 min
2. temperaturecooled to room temperature
3. temperatureAt this time, the reaction was cooled to 0° C.
4. customthe reaction to pH=8
5. filtrationwas filtered over celite
6. washwashed well with ethyl acetate (500 mL)
7. customThe water layer and the organic layer were separated
8. extractionThe aqueous layer was extracted with ethyl acetate (2×500 mL)
9. washThe combined organics were washed with water (1×400 mL)
10. dry with materiala saturated aqueous sodium chloride solution (1×400 mL), dried with magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated under vacuum
13. customThe resulting oil was purified by column chromatography
14. washeluted with petroleum ether

ORD record

ord-b8d4bf86ab164b07adcd3b4dc1a50a8a

Source dataset

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07807674B2