1441673-92-2

1129634-44-1

1441673-92-2

E. Potassium salt formation (S)-5-(tert-butoxycarbonyl)-5-azaspiro[2.4]heptane-6-carboxylic acid (219 g) was dissolved in 2-methyltetrahydrofuran (880 mL) and the solution was subsequently heated to 35 °C. A THF solution of 1.0 M potassium tert-butanolate (1.05 L) was slowly added while maintaining an internal temperature not exceeding 40 °C. The reaction mixture was stirred for about 30 minutes, followed by slow cooling to 20°C over about 2 hours. After aging at 20 °C for 1 h, a filtration operation was performed. The filter cake was washed with 2-methyltetrahydrofuran (715 mL). The resulting solid was placed in a vacuum oven and dried at 40 °C for 24 h to give potassium (S)-5-(tert-butoxycarbonyl)-5-azaspiro[2.4]heptane-6-carboxylate (212 g, 86% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 4.07 (t, J = 7.3 Hz, 1H), 3.44 (d, J = 10.4 Hz, 1H), 3.35 (s, 1H), 3.10 (d, J = 10.4 Hz, 1H), 2.03 (dd, J = 12.3, 6.9 Hz, 1H), 1.89 (dd, J = 12.3, 8.0 Hz, 1H), 1.38 (s, 9H), 0.71-0.27 (m, 4H). 1H NMR (400 MHz, d6-DMSO) δ: 3.89 (dd, J = 8.6, 4.1 Hz, 0.4H, rotary isomer 1), 3.85 (dd, J = 8.6, 4.3 Hz, 0.6H, rotary isomer 2), 3.21-3.07 (m, 2H), 2.00-1.92 (m, 1H), 1.75-1.71 (m, 1H), 1.36 (s, 4H, rotary isomer 1), 1.32 (s, 5H, rotary isomer 2), 0.46-0.37 (m, 4H). 13C NMR (100 MHz, d6-DMSO) δ 174.5, 174.4, 154.1, 153.4, 77.2, 76.9, 62.3, 62.0, 54.1, 53.8, 38.7, 28.4, 28.3, 20.6, 19.9, 18.8, 11.6, 10.5, 10.2.