1,2-Dichloroethane → (+/-)-tert-Butyl 6-(1-cyanocyclopropanecarbonyl)-6-azaspiro[3.4]octan-8-ylcarbamate

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Reaction Steps

A solution of (+/−)-tert-butyl 6-azaspiro[3.4]octan-8-ylcarbamate (from Step 1 of Example 318, 0.177 g, 0.783 mmol), 1-cyanocyclopropanecarboxylic acid (0.104 g, 0.939 mmol), EDC (0.300 g, 1.565 mmol), HOBT (0.144 g, 0.939 mmol), and Hunig's Base (0.547 mL, 3.13 mmol) in DMA (7.67 mL) was stirred @ r. t. under N2 for 16 hrs. +/−MS analysis after 16 hrs indicated that the reaction had proceeded essentially to completion and no starting material was detected. The volatiles were removed under high vacuum. EtOAc, THF, and 10% aq LiCl solution were added. The layers were separated, the organic layer was washed with 10% aq LiCl solution, 1N HCl (3×), sat. aq NaHCO3 solution (3×), brine, dried over Na2SO4, and concentrated under vacuum to yield 0.223 g of the crude product as an orange viscous semi-solid. Flash chromatography on silica gel (Teledyne-Isco RediSep Rf 4 g column), eluting with 100 mL of 75:25 hexane:EtOAc yielded 0.191 g of the title compound as a pale yellow solid. +/−MS: m/e 320.3 (M+H). 318.5 (M−H), 220.2 (M+H-Boc), 264.2 (M+H-isobutylene). This material was used in the next step without further purification.

Provenance & Evidence