Triisopropyl borate → (5-{[(Tert-butoxy-carbonyl)amino]methyl}-2-chloropyridin-4yl)boronic acid

Temperature

-78 °C

Tert-butyl[(6-chloropyridin-3-yl)methyl]carbamate (1.00 g, 0.004 mol) was dissolved in anhydrous tetrahydrofuran (20 mL) in an oven-dried 50-mL round-bottomed flask. The solution was stirred under an atmosphere of nitrogen and cooled to at −78° C. Tert-butyllithium (1.7 M in pentane, 5.1 mL, 0.009 mol) was slowly added via syringe. The reaction solution turned yellow, then dark orange during the addition. The resulting solution was stirred at −77° C. for 10 min, then was slowly warmed to −20° C. Triisopropyl borate (3.79 mL, 0.017 mol) was added quickly via syringe and the mixture was allowed to warm to room temperature with stirring. The reaction was cooled to 0° C. and quenched by the slow addition of 1.00 M of hydrochloric acid in water (8.65 mL) with good stirring. The reaction mixture was then added to water (100 mL) in a separatory funnel and was extracted with ethyl acetate (3×75 mL). The extracts were combined, dried over sodium sulfate, filtered, concentrated and dried under vacuum to leave 1.15 g (97% yield) (5-{[(tert-butoxy-carbonyl)amino]methyl}-2-chloropyridin-4yl)boronic acid as an orange foam. The product structure was confirmed by NMR and MS and used without further purification.

1. additiondark orange during the addition
2. stirringThe resulting solution was stirred at −77° C. for 10 min
3. temperaturewas slowly warmed to −20° C
4. temperatureto warm to room temperature
5. stirringwith stirring
6. temperatureThe reaction was cooled to 0° C.
7. customquenched by the slow addition of 1.00 M of hydrochloric acid in water (8.65 mL) with good stirring
8. additionThe reaction mixture was then added to water (100 mL) in a separatory funnel
9. extractionwas extracted with ethyl acetate (3×75 mL)
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated
13. customdried under vacuum

ORD record

ord-27344f63030f4d3ebed7b1e8ee92e883

Source dataset

uspto-grants-2010_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07718648B2