Triisopropyl borate → 6-Chloropyridine-2-boronic acid

A solution of n-Buli (2.5 M, 24.91 mL, 62.3 mmol) in freshly distilled THF (100 mL) was cooled to −78° C., followed by the addition of a solution of 2-bromo-6-chloropyridine (10.0 g, 51.96 mmol) in 10 mL THF. The resulting dark colored mixture was stirred at this temperature for 45 min. A solution of triisopropylborate (11.72 g, 62.3 mmol) was added and the mixture was stirred at −78° C. for 2 h, and warmed to RT and stirred for an additional 1 h. The mixture was quenched by slow addition of 3% aq NaOH solution (400 mL). The resulting aqueous layer was collected and acidified down to pH 5-6 by dropwise addition of 3N HCl (180 mL), keeping the internal temperature below 5° C. The mixture was extracted with EtOAc and the combined organic layers were dried, filtered and concentrated. The residue was recrystallized from Et2O to give 6-chloropyridin-2-ylboronic acid (6 g, 73.6%) as a white solid. MS (ESI, pos. ion) m/z: 158 (M+1); 1H NMR (DMSO-d6, 300 MHz): δ ppm 8.51 (brs, 1H), 7.84 (m, 2H), 7.51-7.48 (m, 1H).

1. stirringthe mixture was stirred at −78° C. for 2 h
2. stirringstirred for an additional 1 h
3. customThe mixture was quenched by slow addition of 3% aq NaOH solution (400 mL)
4. customThe resulting aqueous layer was collected
5. additionacidified down to pH 5-6 by dropwise addition of 3N HCl (180 mL)
6. customthe internal temperature below 5° C
7. extractionThe mixture was extracted with EtOAc
8. customthe combined organic layers were dried
9. filtrationfiltered
10. concentrationconcentrated
11. customThe residue was recrystallized from Et2O

ORD record

ord-af57deebd5d94b419c37eab879d6ea59

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09321756B2