Potassium hydroxy sulfite → 1261604-72-1

Temperature

0 °C

To a solution of 4-bromo-2-chloro-1-(difluoromethoxy)benzene (Preparation 70, 0.83 g, 3.2 mmol) in THF (16 mL) was added 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi-1,3,2-dioxaborolane (0.90 g, 3.6 mmol), Pd(dppf)Cl2 (0.12 g, 0.16 mmol), and potassium acetate (0.98 g, 9.7 mmol) under a nitrogen atmosphere and the mixture heated at reflux for 2 hours. The reaction mixture was then concentrated in vacuo, the resulting residue filtered through silica gel pad with arbocel and washed EtOAc. The filtrate was concentrated in vacuo to yield a crude product of 2-[3-chloro-4-(difluoromethoxy)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane. A solution of crude 2-[3-chloro-4-(difluoromethoxy)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.0 g, 3.3 mmol) in acetone (10 mL) was added to an aqueous oxone solution (2.6 g, 3.9 mmol, 10 mL) dropwise with stirring at 0° C. for 1 hour. The reaction mixture was partitioned between water (20 mL) and EtOAc (20 mL) and the organic layer was washed with brine, dried over sodium sulphate, filtered, and concentrated in vacuo. The resulting crude was purified by silica gel chromatography eluting with 0 to 40% EtOAc in heptane to afford the title compound as a pale brown oil (0.53 g, 82%):

1. customThe reaction mixture was partitioned between water (20 mL) and EtOAc (20 mL)
2. washthe organic layer was washed with brine
3. dry with materialdried over sodium sulphate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe resulting crude was purified by silica gel chromatography
7. washeluting with 0 to 40% EtOAc in heptane

ORD record

ord-06590d48a2244493a9e79637f2a6c782

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09096500B2