Hydrochloric Acid → 1-(4-Fluorophenyl)-1H-pyrazol-5-ylboronic acid

Temperature

-78 °C

To a stirred solution of commercially available 1-(4-fluorophenyl)-1H-pyrazole [CAS No 81329-32-0] (1.6 g, 9.87 mmol) in THF (39.5 ml) was added drop wise at −78° C. under nitrogen atmosphere N-butyllithium (1.6 N in hexane, 6.47 ml, 10.4 mmol). After the mixture was allowed to stir at −78° C. for 1 h triisopropyl borate (7.65 g, 9.35 ml, 39.5 mmol) was added at −78° C. The mixture was allowed to stir at −78° C. for 1 h, gradually warmed to room temperature, and the pH of the mixture was adjusted to 5 with 1 M HCl solution. The mixture was evaporated and the remaining water layer extracted with ethyl acetate (2×30 ml). The combined organic layers were washed with brine (30 ml), dried over MgSO4 and evaporated. The raw product was purified by column chromatography on silica gel (dichloromethane/MeOH) and trituration (diethyl ether/hexane) to yield the title compound as a white solid (479 mg, 24%), MS (ISN) m/z=205.0 [(M−H)−], mp 115° C.

1. additionwas added at −78° C
2. temperaturegradually warmed to room temperature
3. customThe mixture was evaporated
4. extractionthe remaining water layer extracted with ethyl acetate (2×30 ml)
5. washThe combined organic layers were washed with brine (30 ml)
6. dry with materialdried over MgSO4
7. customevaporated
8. customThe raw product was purified by column chromatography on silica gel (dichloromethane/MeOH) and trituration (diethyl ether/hexane)

ORD record

ord-a21aa21d000449bda4bfebfc4eba66c7

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365550B2