Diisopropylethylamine → Ethyl 2-{4-[(1-methylcyclobutyl)carbamoyl]piperidin-1-yl}-6-azaspiro[3.4]octane-6-carboxylate

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Reaction Steps

1-[6-(Ethoxycarbonyl)-6-azaspiro[3.4]oct-2-yl]piperidine-4-carboxylic acid (0.368 g, 1.10 mmol) was dissolved in DMF (8 mL) and (1-methylcyclobutyl)amine hydrochloride (0.200 g, 1.64 mmol), HATU (0.458 g, 1.21 mmol) and DIPEA (0.708 g, 5.45 mmol) were added. The reaction mixture was stirred at rt overnight under nitrogen. The solvents were removed in vacuo, and the residue was partitioned between DCM and sat. NaHCO3 sol., organic layer washed with sat. NaCl sol. and dried over MgSO4. The solvents were removed in vacuo, and the residue was purified by column chromatography (normal phase, [Biotage SNAP cartridge KP-sil 25 g, 40-63 μm, 60 A, 12 mL per min, gradient 1% to 8% MeOH in DCM]) to give ethyl 2-{4-[(1-methylcyclobutyl)carbamoyl]piperidin-1-yl}-6-azaspiro[3.4]octane-6-carboxylate isomer 2 (0.147 g, 35.5%) as a white foam.

Provenance & Evidence