Water → 1-Chloroethyl 3-(2-(6-bromopyridin-2-yl)-2-methylhydrazono)-8-azabicyclo[3.2.1]octane-8-carboxylate

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Reaction Steps

A solution of 2-bromo-6-(1-methylhydrazinyl)pyridine (1.60 g, 7.90 mmol), 1-chloroethyl 3-oxo-8-azabicyclo[3.2.1]octane-8-carboxylate (1.80 g, 7.90 mmol) and p-toluenesulphonic acid (300 mg, 1.60 mmol) in toluene (50 mL) was heated under reflux, with water removal (azeotrope), for 3 h. The mixture was cooled to room temperature and concentrated. The residue was purified by flash column chromatography (silica gel, 0%-100% solvent mixture B in methylene chloride; solvent mixture B=80:18:2 methylene chloride/methanol/concentrated ammonium hydroxide) to give the title compound (676 mg, 28%) as a yellow solid: 1H NMR (500 MHz, CDCl3) δ 7.31 (t, J=7.5 Hz, 1H), 6.88 (d, J=7.5 Hz, 1H), 6.68-6.65 (m, 1H), 6.62 (d, J=8.0 Hz, 1H), 4.63-4.40 (m, 3H), 3.17 (s, 3H), 2.93-2.90 (m, 1H), 265-2.62 (m, 1H), 2.42-2.37 (dd, J=16.0, 6.0 Hz, 1H), 2.13-2.00 (m, 3H), 1.85 (d, J=6.0 Hz, 3H), 1.80-1.73 (m, 1H).

Provenance & Evidence