Dichloromethane → (4-Cyano-3-fluorophenyl)boronic acid

Temperature

-75 °C

Dissolve 2-Fluoro-4-bromobenzonitrile (200 g, 990 mmol, 1.00 eq.) and triisopropyl borate (228 g, 1188 mmol, 1.2 eq.) in 700 mL of THF and 1400 mL of toluene. Cool the mixture with a dry ice/acetone bath to an internal temperature of −75° C. Slowly add n-BuLi (396 mL of a 2.5 M solution in hexanes) over a period of 2 hours. After addition is complete, a light-red, thin slurry occurs. Let the solution stir at −74° C. for 15 minutes, allow the solution to warm to −20° C. and then quench with 1500 mL of 2.5 M HCl. Let the solution warm to RT. Separate layers, extract the aqueous layer with EtOAc, dry the combined organic phases with Na2SO4, filter and concentrate in vacuo to yield a light-brown solid. Triturate the solid with hexane and transfer to a scintered glass funnel. Rinse with hexane one more time to obtain a pale-yellow filtrate. Stir the light-brown solid with cold CH2Cl2 and filter. Rinse with a small volume of CH2Cl2 to yield an off-white solid and a brown filtrate. Dry the solid in a vacuum oven at 40° C. and dried to yield 112 g (679 mmol, 69%) of 3-fluoro-4-cyanophenylboronic acid as an off-white solid.

1. additionAfter addition
2. temperatureto warm to −20° C.
3. customquench with 1500 mL of 2.5 M HCl
4. temperaturewarm to RT
5. extractionSeparate layers, extract the aqueous layer with EtOAc
6. dry with materialdry the combined organic phases with Na2SO4
7. filtrationfilter
8. concentrationconcentrate in vacuo
9. customto yield a light-brown solid
10. customTriturate the solid with hexane and transfer to a scintered glass funnel
11. washRinse with hexane one more time
12. customto obtain a pale-yellow filtrate
13. filtrationfilter
14. washRinse with a small volume of CH2Cl2
15. customto yield an off-white solid
16. customDry the solid in a vacuum oven at 40° C.
17. customdried

ORD record

ord-f75b71f8374448ac8f875288056935f7

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07932284B2