Hydrochloric Acid → (3,4,5-Trifluorophenyl)boronic Acid (contains varying amounts of Anhydride)

Temperature

32 °C

A nitrogen- or argon-inertized reactor was initially charged with 83.2 g (3.42 mol) of magnesium turnings and then 1646.2 g of dry, unstabilized tetrahydrofuran were added. 30 g (0.14 mol) of 3,4,5-trifluorobromobenzene were added dropwise at 25° C. with stirring and the startup of the Grignard reaction was awaited. The startup of the Grignard reaction was perceptible by a spontaneous temperature increase to approx. 32° C. Subsequently, 571.9 g (2.71 mol) of further 3,4,5-trifluorobromobenzene were metered in at 25-35° C. within 5 h. To complete the reaction, the mixture was stirred at 25-30° C. for a further 2 h. A 2nd reactor was initially charged with a solution of 328.0 g (3.16 mol) of trimethyl borate and 452 g of dry, unstabilized tetrahydrofuran, which were precooled to −5° C. Thereafter, the Grignard solution was metered in from the 1st reactor within 2.5 h. The excess magnesium remained in the 1st reactor. After the metered addition had ended, the mixture was stirred at 20-25° C. for another 2 h. For hydrolysis, 1326.1 g (2.76 mol) of 7.6% hydrochloric acid were then metered in at 25° C., after which the mixture was stirred at 25° C. for another 1 h. The mixture was heated to 50° C. and the phases were separated. Thereafter, the organic phase was re-extracted with 603.9 g of water at 50° C. and the washing water phase was removed again. Subsequently, the organic phase was concentrated by distilling off a tetrahydrofuran/water mixture. This afforded 1032.6 (82%) of a 40% solution of 3,4,5-trifluorophenylboronic acid in tetrahydrofuran, which was used directly for the subsequent reactions.

1. custom1646.2 g of dry
2. additionunstabilized tetrahydrofuran were added
3. customthe startup of the Grignard reaction
4. customThe startup of the Grignard reaction
5. customthe reaction
6. stirringthe mixture was stirred at 25-30° C. for a further 2 h
7. customof dry
8. customwere precooled to −5° C
9. additionAfter the metered addition
10. stirringthe mixture was stirred at 20-25° C. for another 2 h
11. customwere then metered in at 25° C.
12. stirringafter which the mixture was stirred at 25° C. for another 1 h
13. temperatureThe mixture was heated to 50° C.
14. customthe phases were separated
15. extractionThereafter, the organic phase was re-extracted with 603.9 g of water at 50° C.
16. customthe washing water phase was removed again
17. concentrationSubsequently, the organic phase was concentrated
18. distillationby distilling off a tetrahydrofuran/water mixture

ORD record

ord-e9fa9c8da4f84428b4c853a35ed2de2a

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08461390B2