Hydrochloric Acid → (4-Butoxy-2,3-difluorophenyl)boronic acid

The compound (22) (84.6 g) and THF (500 ml) were put in a reaction vessel under a nitrogen atmosphere, and cooled to −74° C. n-Butyllithium (1.65 M in a n-hexane solution; 303.0 ml) was added dropwise in the temperature range of −74° C. to −70° C., and the stirring was continued for another 2 hours. Then, the mixture was added dropwise to a THF (200 ml) solution of trimethyl borate (56.7 g) in the temperature range of −74° C. to −65° C., and the stirring was continued for another 8 hours while the mixture was allowed to return to 25° C. Subsequently, the reaction mixture was poured into a vessel containing 1N—HCl (100 ml) and ice-water (500 ml), and mixed. Ethyl acetate (300 ml) was added thereto and the mixture was allowed to separate into organic and aqueous phases, and the extraction was carried out. The organic phase obtained was washed sequentially with water, a saturated aqueous solution of sodium hydrogencarbonate and brine, and dried over anhydrous magnesium sulfate. Then the solvent was distilled off under reduced pressure, giving 4-butoxy-2,3-difluorophenylboronic acid (23) (6.4 g). The yield based on the compound (22) was 69.2%.

1. addition303.0 ml) was added dropwise in the temperature range of −74° C. to −70° C.
2. waitthe stirring was continued for another 8 hours while the mixture
3. customto return to 25° C
4. additionSubsequently, the reaction mixture was poured into a vessel
5. additionmixed
6. customto separate into organic and aqueous phases
7. extractionthe extraction
8. customThe organic phase obtained
9. washwas washed sequentially with water
10. dry with materiala saturated aqueous solution of sodium hydrogencarbonate and brine, and dried over anhydrous magnesium sulfate
11. distillationThen the solvent was distilled off under reduced pressure

ORD record

ord-e00fdaca00c34136bc2cfc9d56cf938c

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08216489B2