Dichloromethane → Ethyl 3-amino-6-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)pyridine-2-carboxylate

Participants

Reaction Steps

A mixture of 3-amino-6-bromopyridine-2-carboxylic acid ethyl ester- (Compound 232G, 0.31 g, 1.3 mmol), 1,4-dioxaspiro[4,5]dec-7-ene-8-boronic acid pinacol ester (0.406 g, 1.52 mmol) and [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (0.10 g, 0.12 mmol) in a 35 mL sealable microwave tube was taken up in 1,4-Dioxane (4.9 mL). This mixture was treated with a solution of Potassium carbonate (0.52 g, 3.8 mmol) in H2O (1 mL), flushed with nitrogen, sealed and irradiated in a microwave reactor for 30 minutes at 100° C. The mixture was poured into water and extracted twice with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4 filtered and concentrated to a brown residue. This was taken up in DCM, treated with silica and concentrated. The resulting silica plug was loaded on to a sample cartridge and purified on an ISCO Combiflash system (0-50% EtOAc/Heptane) to isolate the desired product as 247 mg of an oil which crystallized upon standing. 1H NMR (400 MHz, DMSO-d6) δ 1.30 (t, J=7.20 Hz, 3H), 1.77 (t, J=6.44 Hz, 2H), 2.32-2.40 (m, 2H), 2.60 (td, J=6.44, 1.52 Hz, 2H), 3.91 (s, 4H), 4.28 (q, J=7.07 Hz, 2H), 6.25 (t, J=4.04 Hz, 1H), 6.65 (s, 2H), 7.17 (d, J=8.84 Hz, 1H), 7.52 (d, J=8.84 Hz, 1H). MS (ES+): m/z=305.12 (100) [M+1]. HPLC: tR=3.50 min (ZQ3, polar—5 min).

Provenance & Evidence