Isopropanol → 5-Bromo-2-(1-methylethoxy)pyridine

Temperature

60 °C

60% NaH in oil (1.5:1, Sodium hydride:Mineral Oil, 5.20 g) was added in two portions to isopropyl alcohol (150 mL) at room temperature under N2. The mixture was stirred at 60° C. for 30 min. 5-bromo-2-chloropyridine (10.00 g, 51.96 mmol) was added in two portions and the mixture was stirred at reflux 4 h and then at 80° C. overnight. The solution was concentrated in vacuo. Water (50 mL) and EtOAc (50 mL) was added and the layers were separated. The aqueous layer was extracted with EtOAc (50 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and the solvent was removed in vacuo. The crude product was subjected to flash chromatography (silica, 0-50% EtOAc in heptanes) to give the title compound as a clear oil (8.74 g, 78%). 1H NMR (600 MHz, DMSO) δ 8.17 (s, 1H), 7.61 (dd, 1H), 6.59 (d, 1H), 5.23 (m, 1H), 1.33 (s, 6H).

1. stirringthe mixture was stirred
2. temperatureat reflux 4 h
3. customat 80° C.
4. customovernight
5. concentrationThe solution was concentrated in vacuo
6. additionWater (50 mL) and EtOAc (50 mL) was added
7. customthe layers were separated
8. extractionThe aqueous layer was extracted with EtOAc (50 mL)
9. washThe combined organic layers were washed with brine
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. customthe solvent was removed in vacuo

ORD record

ord-9f782caed5e1455b92e4b03b0ecea0a4

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08598213B2