Diisopropylamine → 2-(4-Chloro-2-fluoro-3-(1-fluoroethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Temperature

-78 °C

A 2.5 M solution of n-butyllithium (13 mL, 33 mmol) was added to a stirred solution of diisopropylamine (5.0 mL, 35 mmol) in tetrahydrofuran THF (50 mL) at −78° C. The resulting colorless solution was stirred at −78° C. for 20 m, warmed to 0° C. for 20 m, and then cooled back to −78° C. for 20 m. A solution of 1-chloro-3-fluoro-2-(1-fluoroethyl)benzene (4.8 g, 27 mmol, 1.0 equiv) in THF (20 mL) at −78° C. was transferred to the base solution via cannula. The resulting dark brown solution was stirred at −78° C. for 2 h. 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (8.3 mL, 41 mmol, 1.5 equiv) was added and the brown solution was slowly warmed to 23° C. over 20 h. The reaction mixture was diluted with 0.1M hydrochloric acid (300 mL) and extracted with dichloromethane three times. The combined organic layers were dried, filtered and concentrated by rotary evaporation to afford the title compound as a brown oil that solidified into a semi-solid upon standing (7.7 g, 94% yield). 1H NMR (300 MHz, CDCl3) δ 7.62 (m, 1H), 7.17 (m, 1H), 6.13 (dq, 1H, J=6, 46 Hz), 1.75 (ddd, 3H, J=1, 7, 23 Hz), 1.36 (s, 12H).

1. temperaturewarmed to 0° C. for 20 m
2. temperaturecooled back to −78° C. for 20 m
3. customat −78° C.
4. stirringThe resulting dark brown solution was stirred at −78° C. for 2 h
5. temperaturethe brown solution was slowly warmed to 23° C. over 20 h
6. extractionextracted with dichloromethane three times
7. customThe combined organic layers were dried
8. filtrationfiltered
9. concentrationconcentrated by rotary evaporation

ORD record

ord-a547b83b559a44598a3a60ce77a7a1f4

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08609592B2