Tetrahydrofuran → {5-[(Propan-2-yl)oxy]pyridin-3-yl}boronic acid

Temperature

-78 °C

To a stirred, −78° C. solution of 2.5 M n-butyllithium (44.0 mL, 110 mmol) in toluene (120 mL) was slowly added a solution of 3-bromo-5-isopropoxypyridine (21.6 g, 100 mmol) in toluene (40 mL) while maintaining the temperature below −50° C. After the addition was complete, the reaction was stirred at −78° C. for 30 min. Distilled THF (40 mL) was added, and the reaction stirred for 15 min at −78° C., followed by the addition of triisopropylborate (27.7 mL, 120 mmol) in one portion. After warming to −15° C., the reaction was quenched with 1M HCl (260 mL), and stirred for one hour. The mixture was then neutralized (to pH 7) with 5 M NaOH and extracted with THF (4×100 mL). The combined extracts were dried (Na2SO4), filtered and concentrated. The residue was dissolved in 1:1 THF/MeOH, filtered, concentrated, and dissolved in warm acetonitrile. Upon cooling, the acetonitrile solution deposited a light brown powder, which was collected by filtration and vacuum dried (8.94 g, 49%).

1. temperaturewhile maintaining the temperature below −50° C
2. additionAfter the addition
3. stirringthe reaction stirred for 15 min at −78° C.
4. temperatureAfter warming to −15° C.
5. customthe reaction was quenched with 1M HCl (260 mL)
6. stirringstirred for one hour
7. extractionextracted with THF (4×100 mL)
8. dry with materialThe combined extracts were dried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated
11. dissolutionThe residue was dissolved in 1:1 THF/MeOH
12. filtrationfiltered
13. concentrationconcentrated
14. dissolutiondissolved in warm acetonitrile
15. temperatureUpon cooling
16. filtrationwas collected by filtration and vacuum
17. customdried (8.94 g, 49%)

ORD record

ord-7c0b990a1db84ff08500a98eedcfef63

Source dataset

uspto-grants-2008_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07384929B2