Triisopropyl borate → 4-Methylpyridine-3-Boronic Acid

Temperature

-78 °C

To a stirring solution of 3-bromo-4-methylpyridine (5.9 g, 34.3 mmol) in toluene (30 mL) and THF (7.5 mL) was added triisopropyl borate (10.3 mL, 44.6 mmol). The resulting mixture was cooled to −78° C. under a nitrogen atmosphere followed by the addition of n-butyllithium (17.83 mL, 44.6 mmol, 2.5 M in hexanes) over a period of 1 hour. The reaction mixture was allowed to stir for an additional 30 min and then the dry ice bath was removed. The reaction mixture was quenched by the addition of 2N HCl (60 mL). Upon reaching room temperature, the resulting yellow solution was transferred to a 500 mL separatory funnel and the layers were separated. The aqueous layer was neutralized to pH 7.0 with sodium hydroxide and then extracted with THF (3×60 mL). The combined organics were washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting solid material was vigorously stirred with acetonitrile and filtered to yield Intermediate 1A (2.2 g, 16.06 mmol, 48.8% yield) as an off-white solid. MS (ES): m/z=138.0 [M+H]+. 1H NMR (400 MHz, MeOD) δ ppm 8.45 (1 H, s), 8.33 (1 H, d, J=5.77 Hz), 7.50 (1 H, d, J=5.27 Hz), 2.62 (3 H, s).

1. customthe dry ice bath was removed
2. customThe reaction mixture was quenched by the addition of 2N HCl (60 mL)
3. customUpon reaching room temperature
4. customthe resulting yellow solution was transferred to a 500 mL separatory funnel
5. customthe layers were separated
6. extractionextracted with THF (3×60 mL)
7. washThe combined organics were washed with brine
8. dry with materialdried over anhydrous sodium sulfate
9. concentrationconcentrated under reduced pressure
10. stirringThe resulting solid material was vigorously stirred with acetonitrile
11. filtrationfiltered

ORD record

ord-4835319bf09e4680b5929bd888344a8d

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08916553B2