Dichloromethane → 5-(Chloromethyl)-2-methoxypyridine

To a solution of the above compound (0.105 g, 0.261 mmol) in a mixture of 2 mL of THF and 0.20 mL of water under an atmosphere of nitrogen was added 5-(chloromethyl)-2-methoxypyridine hydrochloride (0.0.066 g, 0.34 mmol), cesium carbonate (0.340 g, 1.04 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloro-palladium(II), 1:1 complex with dichloromethane (0.021 g, 0.026 mmol). The mixture was irradiated in a microwave reactor at 100° C. for 30 min, cooled to rt, and filtered through celite, washing with ethyl acetate. The filtrate was concentrated in vacuo and purified via silica gel chromatography, eluting with 45-100% ethyl acetate in hexanes, to provide the title compound that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 398.0 for [M+H]+: 1H NMR (400 MHz, d6-DMSO) δ 8.32 (d, J=8.1 Hz, 1H), 8.04 (s, 1H), 7.52 (s, 1H), 7.49-7.47 (m, 1H), 6.78 (d, J=8.6 Hz, 1H), 4.97 (d, J=5.7 Hz, 1H), 3.95 (s, 2H), 3.83 (s, 3H), 3.81-3.71 (m, 2H), 3.60-3.52 (m, 1H), 3.05-3.00 (m, 1H), 2.91 (br s, 2H), 2.74 (br s, 2H), 1.99-1.75 (m, 3H), 1.66-1.55 (m, 1H).

1. customThe mixture was irradiated in a microwave reactor at 100° C. for 30 min
2. filtrationfiltered through celite
3. washwashing with ethyl acetate
4. concentrationThe filtrate was concentrated in vacuo
5. custompurified via silica gel chromatography
6. washeluting with 45-100% ethyl acetate in hexanes

ORD record

ord-acc327e5b0be4fb1a8afbd4baab88802

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08815902B2