Diisopropylamine → 6-Fluoro-2,3'-bipyridin-5-ylboronic acid

Temperature

-78 °C

A stirred solution of diisopropylamine (0.531 ml, 3.79 mmol) (Aldrich) in THF (4 mL) was treated with 1.6 M n-butyllithium in hexanes (2.368 ml, 3.79 mmol) (Aldrich) at −40° C. and the pale yellow solution was stirred for 1 h and then cooled to −78° C. A solution of 6-fluoro-2,3′-bipyridine (550 mg, 3.16 mmol) in THF (5 mL) was added by cannula slowly over 2 min. The resulting bright orange solution was stirred at −78° C. for 1.5 h and then a solution of triisopropyl borate (1.089 ml, 4.74 mmol) (Aldrich) in THF (4 mL) was added slowly. The resulting mixture was stirred at −78° C. for 30 min and then the cooling bath was removed. After the reaction mixture had warmed up to room temperature, the yellow heterogeneous mixture was quenched with 1 N NaOH(aq) (10 mL) and stirred for 30 min. The separated aqueous layer was removed and carefully acidified with 5N HCl until acidic (pH 5 about 6) and the resulting cloudy mixture was extracted with EtOAc (20 mL). Most of the product remained in the aqueous phase so the water was removed on the freeze-dryer overnight resulting in a white fluffy product contaminated with salt. m/z (ESI, +ve ion) 219.1 (M+H)+. 1H NMR (400 MHz, MeOH) δ 9.22 (1H, s); 8.62 (1H, d, J=4.5 Hz); 8.51 (1H, d, J=8.0 Hz); 8.12 (1H, t, J=7.9 Hz); 7.89 (1H, dd, J=7.3, 2.8 Hz); 7.59 (1H, dd, J=8.0, 4.9 Hz).

1. stirringThe resulting bright orange solution was stirred at −78° C. for 1.5 h
2. stirringThe resulting mixture was stirred at −78° C. for 30 min
3. customthe cooling bath was removed
4. temperatureAfter the reaction mixture had warmed up to room temperature
5. customthe yellow heterogeneous mixture was quenched with 1 N NaOH(aq) (10 mL)
6. stirringstirred for 30 min
7. customThe separated aqueous layer was removed
8. extractionthe resulting cloudy mixture was extracted with EtOAc (20 mL)
9. customwas removed on the freeze-dryer overnight
10. customresulting in a white fluffy product

ORD record

ord-39f99bfa38b9445fbb3e8602a408692f

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08772480B2