2-Bromo-5-methylpyridine → tert-Butyl 3-(5-methylpyridin-2-yl)azetidine-1-carboxylate

To a solution of N-Boc-3-iodoazetidine (126-1) (500 mg, 1.77 mmol) in THF (5 mL) was added a solution of Reike Zinc (1.4 mL, 0.1 g/mL in THF, 2.2 mmol); a slight exotherm was noted upon addition of the zinc. After stirring for 1 h at room temperature, a solution of 2-bromo-5-methylpyridine (304 mg, 1.77 mmol) in THF (2 mL) was added, followed by bis(tri-tert-butylphosphine)palladium(0) (90 mg, 0.17 mmol) and the reaction was heated at 75° C. for 2 h. After stirring for 16 h at room temperature, the reaction was filtered through Celite, rinsing with EtOAc. The filtrate was washed with aqueous NaHCO3 (sat.) and brine, and the organic layer was dried over Na2SO4, filtered, and concentrated. The crude residue was purified by silica gel chromatography (EtOAc/hexane) to provide 126-2 as a colorless oil. MS: m/z=249.4 (M+H).

1. temperaturethe reaction was heated at 75° C. for 2 h
2. stirringAfter stirring for 16 h at room temperature
3. filtrationthe reaction was filtered through Celite
4. washrinsing with EtOAc
5. washThe filtrate was washed with aqueous NaHCO3 (sat.) and brine
6. dry with materialthe organic layer was dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude residue was purified by silica gel chromatography (EtOAc/hexane)

ORD record

ord-727686f9f1f84948bccfe6f42f96d8ad

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365562B2