Tetrahydrofuran → (R)-2-(3,4-Difluorophenyl)-4-[3-(tert-butyldimethylsiloxy)-1-butoxy]-5-bromo-3(2H)-pyridazinone

To a stirred, 0° C. solution of the product from Example 545B (3.4 g, 10 mmol) in THF (20 mL) was added 1M sodium bis(trimethylsilyl)amide in THF (12 mL, 12 mmol). The reaction mixture was stirred at room temperature for 0.5 hours, then it was transferred to a stirred, −30° C. solution of 2-(3,4-difluorophenyl)-4,5-dibromo-3(2H)-pyridazinone (3.66 g, 10 mmol) in THF (100 mL). The reaction mixture was stirred at −30° C. for 1 hour, then overnight while warming to room temperature. The reaction was quenched with saturated aqueous ammonium chloride solution (100 mL) and extracted with ethyl acetate (2×100 mL). The organic layer was washed with brine (2×20 mL), then dried (MgSO4), and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (silica gel, 90:10 hexane/ethyl acetate) to provide the title intermediate (2.5 g, 51%).

1. stirringThe reaction mixture was stirred at −30° C. for 1 hour
2. temperatureovernight while warming to room temperature
3. customThe reaction was quenched with saturated aqueous ammonium chloride solution (100 mL)
4. extractionextracted with ethyl acetate (2×100 mL)
5. washThe organic layer was washed with brine (2×20 mL)
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationThe filtrate was concentrated under reduced pressure
9. customthe residue was purified by column chromatography (silica gel, 90:10 hexane/ethyl acetate)

ORD record

ord-a77db14771ed42bcb9bb31c71dc7defd

Source dataset

uspto-grants-2001_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06307047B1