Tetrahydrofuran → 2-Chloropyridine-5-boronic acid

Temperature

-78 °C

In a flask replaced by nitrogen, tetrahydrofuran solution (80 g) containing 5-bromo-2-chloropyridine (9.6 g, 50.0 mmol) was charged, and cooled at −78° C., and then n-hexane solution of n-butyllthium (15% by weight, 24.6 g, 57.5 mmol) was added dropwise at −78° C. Next, at −78° C., trimethoxyborane (5.7 g, 55.0 mmol) was added dropwise. After 30 minutes from adding dropwise, cooling bath was removed off, and the reaction mixture was stirred at room temperature overnight. Then, 10% by weight of hydrochloric acid (50 g) was added under ice cooling condition, and the reaction mixture was stirred for 1.5 hours, and then neutralized by adding 40% by weight of sodium hydroxide aqueous solution (15 g). Ethyl acetate (50 g) was added to the reaction mixture, and the reaction mixture was stirred for 1.0 hour, and then left to stand to separate organic layer. Organic layer was dried with anhydrous magnesium sulfate, and then condensed under reduced pressure to obtain 6-chloro-3-pyridylboronic acid (6.9 g, 44.0 mmol).

1. additionwas charged
2. additionAfter 30 minutes from adding dropwise
3. temperaturecooling bath
4. customwas removed off
5. additionThen, 10% by weight of hydrochloric acid (50 g) was added under ice cooling condition
6. stirringthe reaction mixture was stirred for 1.5 hours
7. additionby adding 40% by weight of sodium hydroxide aqueous solution (15 g)
8. additionEthyl acetate (50 g) was added to the reaction mixture
9. stirringthe reaction mixture was stirred for 1.0 hour
10. waitleft
11. customto separate organic layer
12. dry with materialOrganic layer was dried with anhydrous magnesium sulfate
13. customcondensed under reduced pressure

ORD record

ord-ef21a8a45b9c4950bbe84a4e5f3b1dd6

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08742127B2