Sodium hydride → 4-Bromo-6-chloro-2-((2-(trimethylsilyl)ethoxy)methyl)pyridazin-3(2H)-one

Temperature

0 °C

A 500-mL single-neck round-bottomed flask equipped with a magnetic stirrer was purged with nitrogen and charged with anhydrous DMF (150 mL) and 4-bromo-6-chloro-pyridazin-3(2H)-one (10.0 g, 47.8 mmol). The reaction mixture was cooled to 0° C. and sodium hydride was added. The reaction was stirred at 0° C. for 20 min. After this time, 2-(trimethylsilyl)ethoxymethyl chloride (11.9 g, 71.6 mmol) was added and the cooling bath was removed, and the reaction was stirred at room temperature for 3 h. The reaction was then quenched with saturated aqueous sodium bicarbonate (30 mL). The mixture was extracted with ethyl acetate (2×300 mL). The extracts were dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash chromatography to afford 253a in a 56% yield (9.00 g) as a yellow oil: 1H NMR (300 MHz, CDCl3) δ 8.02 (s, 1H), 5.42 (s, 2H), 3.79 (t, 2H, J=5.4 Hz), 0.96 (t, 2H, J=5.4 Hz), 0.01 (s, 9H).

1. customA 500-mL single-neck round-bottomed flask equipped with a magnetic stirrer
2. customwas purged with nitrogen
3. customthe cooling bath was removed
4. stirringthe reaction was stirred at room temperature for 3 h
5. customThe reaction was then quenched with saturated aqueous sodium bicarbonate (30 mL)
6. extractionThe mixture was extracted with ethyl acetate (2×300 mL)
7. dry with materialThe extracts were dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe resulting residue was purified by flash chromatography

ORD record

ord-b4e82028cc5e42a19e0c786d01d67d19

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09238655B2