[H-].[Na+].[C:3]([N:22]1[N:26]=[N:25][C:24]([CH2:27][C:28]#[N:29])=[N:23]1)([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C1(=O)CCCCC1.[I-].C[S+](C)(C)=O.[C:43]1(=[C:49](C2N=NN(C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)N=2)C#N)[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]1>C1COCC1.CN(C=O)C>[C:3]([N:22]1[N:26]=[N:25][C:24]([C:27]2([C:28]#[N:29])[C:43]3([CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]3)[CH2:49]2)=[N:23]1)([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1To a flask charged with dry sodium hydride (0.34 g, 14.1 mmol) was added (2-trityl-2H-tetrazol-5-yl)-acetonitrile (2.49 g, 7.10 mmol). The solids were swirled to mix, cooled to 0° C., and 25 mL THF was added quickly, resulting in vigorous H2 evolution and a bright yellow foam. The mixture was stirred at 0° C. for 5 min, at which time the ice bath was removed and stirring continued for 10 min. Cyclohexanone (0.81 mL, 7.80 mmol) in 10 mL THF was added quickly resulting in a clear orange solution. The mixture was stirred for 2 h, partitioned between EtOAc and sat. NH4Cl (aq), and the organic phase dried (MgSO4) and concentrated. Meanwhile, to trimethylsulfoxonium iodide (2.48 g, 11.2 mmol) in 25 mL DMF was added sodium hydride (60% dispersion in mineral oil, 0.45 g, 11.2 mmol). The mixture was stirred for 30 min at which time a suspension of crude cyclohexylidene-(2-trityl-2H-tetrazol-5-yl)-acetonitrile (ca. 7.5 mmol) in 15 mL DMF was added quickly dropwise. The orange solution was stirred overnight, partitioned between EtOAc and H2O, and the phases separated. The organic phase was washed with brine, dried (MgSO4) and concentrated. Flash chromatography of the residue (CH2Cl2) provided 2.43 g (77%, two steps) of 1-(2-trityl-2H-tetrazol-5-yl)-spiro[2.5]octane-1-carbonitrile as a colorless foam. 1H NMR (CDCl3) δ 7.32 (m, 9H), 7.08 (m, 6H), 1.99 (d, J=5.4 Hz, 1H, cyclopropyl —CHH), 1.80 (m, 2H), 1.72 (m, 2H), 1.59 (d, J=5.4 Hz, 1H, cyclopropyl —CHH), 1.51 (m, 1H), 1.41 (m, 1H), 1.29 (m, 3H), 1.09 (m, 2H), 0.83 (m, 1H).
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