Diisopropylethylamine → Ethyl 3-{4-methoxy-4-[(1-methylcyclobutyl)carbamoyl]piperidin-1-yl}-8-azabicyclo[3.2.1]octane-8-carboxylate

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Reaction Steps

1-[8-(Ethoxycarbonyl)-8-azabicyclo[3.2.1]oct-3-yl]-4-methoxypiperidine-4-carboxylic acid (0.093 g, assumed 0.27 mmol) was dissolved in DMF (5 mL) and (1-methylcyclobutyl)amine hydrochloride (0.05 g, 0.411 mmol), HATU (0.156 g, 0.41 mmol) and DIPEA (0.177 g, 0.24 mL, 1.37 mmol) were added. The reaction mixture was stirred at rt for 60 h and the solvents were removed in vacuo. The residue was partitioned between DCM and sat. NaHCO3 sol., the organic layer was washed with sat. NaCl sol. and dried (MgSO4). The solvents were removed in vacuo, and the residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 10 g, 40-63 μm, 60 A, 25 mL per min, gradient 0% to 10% MeOH in DCM]) to give ethyl 3-{4-methoxy-4-[(1-methylcyclobutyl)carbamoyl]piperidin-1-yl}-8-azabicyclo[3.2.1]octane-8-carboxylate isomer 1 (0.028 g, 25%) as a pale yellow gum.

Provenance & Evidence