[C:1]([O:5][C:6](=[O:20])[NH:7][CH2:8][C:9]1([C:17](=O)[NH2:18])[C:11]2([CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[CH2:10]1)([CH3:4])([CH3:3])[CH3:2].N1C(Cl)=NC(Cl)=NC=1Cl.[OH-].[Na+]>CN(C=O)C>[C:1]([O:5][C:6](=[O:20])[NH:7][CH2:8][C:9]1([C:17]#[N:18])[C:11]2([CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[CH2:10]1)([CH3:4])([CH3:2])[CH3:3](1-carbamoyl-spiro[2.5]oct-1-ylmethyl)-carbamic acid tert-butyl ester (13.1 g, 46.4 mmol) was suspended in DMF (400 mL) and cooled in an ice bath. Cyanuric chloride (11.8 g, 64.9 mmol) was added. After 20 minutes the solution was homogeneous and after 30 minutes a new precipitate began to form. After 1 hour, the mixture was poured over 0.5N NaOH (500 mL) with ice bath cooling and then transferred to a separatory funnel. The solution was extracted with ethyl acetate (3×400 mL). The combined organic layers were washed with brine (2×400 mL), dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue was dissolved in ethyl acetate (300 mL), washed with brine (3×300 mL), dried over sodium sulfate, filtered and evaporated to give 12.1 g (98%) of (1-cyano-spiro[2.5]oct-1-ylmethyl)-carbamic acid tert-butyl ester as an off-white solid: 1H NMR (300 MHz, CDCl3) δ 0.96 (d, J=5.2 Hz, 1H), 1.07 (d, J=5.2 Hz, 1H), 1.46 (s, 9H), 1.4-1.7 (m, 10H), 3.40 (m, 2H), 4.95 (s, 1H); MS (APCI) m/z 263 [M−H]−.
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