Hydrochloric Acid → (R)-(4-(1-(Benzyloxy)-3-fluoropropan-2-yl)-3-methylphenyl)boronic acid

Temperature

-78 °C

To a solution of 24B (0.46 g, 1.364 mmol) in THF (7 mL) at −78° C., was added a solution of n-BuLi (2.2 mL, 3.52 mmol) dropwise. The mixture was stirred at −78° C. for 15 min, then was treated with trimethyl borate (0.456 mL, 4.09 mmol). The reaction was stirred at −78° C. for 15 min, then was allowed to warm to rt and stir for 3 h. The reaction mixture was diluted with EtOAc (30 mL), treated with 1N HCl (20 mL). The mixture was stirred at rt for 1 h. The phases were separated, then the aqueous layer was extracted with EtOAc. The combined organic phase was washed with H2O and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 80% EtOAc/hexanes) to give 24C (0.2 g, 0.662 mmol, 48.5% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 7.97-8.10 (m, 2H) 7.28-7.44 (m, 6H) 4.82 (d, J=5.56 Hz, 1H) 4.71 (d, J=5.56 Hz, 1H) 4.53-4.59 (m, 2H) 3.56-3.90 (m, 3H) 2.47 (s, 3H); 19F NMR (376 MHz, chloroform-d) δ ppm −223.99 (s, 1F).

1. stirringThe reaction was stirred at −78° C. for 15 min
2. temperatureto warm to rt
3. stirringstir for 3 h
4. stirringThe mixture was stirred at rt for 1 h
5. customThe phases were separated
6. extractionthe aqueous layer was extracted with EtOAc
7. washThe combined organic phase was washed with H2O and brine
8. dry with materialdried (Na2SO4)
9. concentrationconcentrated
10. customThe crude product was purified by flash chromatography (0 to 80% EtOAc/hexanes)

ORD record

ord-52de61dbaff4442591985513fd49a2ca

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09174974B2