Hydrochloric Acid → 5-Methoxypyridine-3-boronic Acid

Temperature

-40 °C

Triisopropyl borate (29.3 mL, 128 mmol) was added over 2 min to a solution of 5-methoxy-3-bromopyridine (20.00 g, 106.4 mmol) in toluene (140 mL) and tetrahydrofuran (35 mL) at −40° C. To this solution was added 2.5 M n-BuLi (51.1 mL, 128 mmol) drop-wise over 35 min while maintaining the temperature at −40° C. After the addition was complete, the reaction was stirred an additional 30 min at −40° C. and then was warmed to −15° C. over one hour. Into the reaction was poured 1 N HCl (175 mL), and the mixture was stirred vigorously for 30 minutes. The layers were separated, and the organic washed once with water (15 mL). The aqueous phases were combined and neutralized (to pH 7) with 5 N NaOH, at which point the boronic acid precipitated out. The biphasic mixture was extracted with THF (3×150 mL). The organic phases were combined, dried over sodium sulfate, filtered, and concentrated to yield 15.36 g of 5-methoxy-3-pyridinylboronic acid as a light brown solid (94%).

1. additionAfter the addition
2. temperaturewas warmed to −15° C. over one hour
3. stirringthe mixture was stirred vigorously for 30 minutes
4. customThe layers were separated
5. washthe organic washed once with water (15 mL)
6. customat which point the boronic acid precipitated out
7. extractionThe biphasic mixture was extracted with THF (3×150 mL)
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated

ORD record

ord-f6e7b22a00b546fd990f9e53c1400b4c

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07897611B2