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tert-Butyl 7-Oxo-2-azaspiro[4.4]nonane-2-carboxylate is a useful reagent for preparing inhibitors of the menin-MLL interaction.

7-Hydroxy-2-azaspiro[4.4]nonane-2-carboxylic acid tert-butyl ester (2.10 g, 8.70 mmol) was used as starting material and suspended in anhydrous dichloromethane (25 mL). Dess-Martin oxidizer (4.43 g, 10.44 mmol) was added to the suspension at 0 °C and under nitrogen protection. Subsequently, the reaction mixture was warmed to room temperature and stirred overnight. Upon completion of the reaction, the mixture was cooled to 0 °C, diluted by the addition of dichloromethane (50 mL), and then quenched by the addition of saturated aqueous sodium bicarbonate (30 mL) and saturated aqueous sodium thiosulfate (30 mL), in that order. The organic phase was separated and washed again with a mixture of saturated aqueous sodium bicarbonate solution (15 mL) and saturated aqueous sodium thiosulfate solution (15 mL). The aqueous phase was back-extracted with dichloromethane (50 mL × 3). All organic phases were combined, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, and filtered. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate, v/v = 3/1) to afford tert-butyl 7-oxo-2-azaspiro[4.4]nonane-2-carboxylate as a yellow liquid (1.30 g, 62% yield). Mass spectrum (ESI, positive ion mode) m/z: 184.2 [(M-C4H8)+ H]+; 1H NMR (600 MHz, CDCl3) δ (ppm): 3.56-3.36 (m, 2H), 3.36-3.24 (m, 2H), 2.39-2.32 (m, 2H), 2.32-2.19 (m, 2H), 2.04 -1.91 (m, 2H), 1.90-1.82 (m, 2H), 1.47 (s, 9H).

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