N[OH:2].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][C:11]1[CH:12]=[C:13]([CH:16]=[CH:17][CH:18]=1)[C:14]#[N:15].[C:19]([N:26]1C=CN=C1)(N1C=CN=C1)=[O:20].O>C(O)(C)C.O1CCOCC1>[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][C:11]1[CH:12]=[C:13]([C:14]2[NH:26][C:19](=[O:20])[O:2][N:15]=2)[CH:16]=[CH:17][CH:18]=1
Add 50% aqueous hydroxylamine (9.73 g, 147 mmol) dropwise to a refluxing solution of 3-(tetrahydro-pyran-2-yloxymethyl)-benzonitrile (8.00 g, 36.8 mmol) in isopropanol (0.1M). After 2 hours, cool to room temperature and concentrate under reduced pressure to give a residue. Dissolve the residue in dioxane (0.1M). Add carbonyldiimidazole (7.16 g, 44.2 mmol) and heat to 110° C. After 30 minutes, cool to room temperature and pour into water. Extract with ethyl acetate. Combine the organic layers, dry with sodium sulfate, filter and concentrate under reduced pressure to yield the title product as a white solid (90.10 g, 89%): 1H NMR (CDCl3) δ 1.53-1.95 (m, 6H), 3.59 (m, 1H), 3.93 (m, 1H), 4.58 (d, 1H), 4.77 (t, 1H), 4.88 (d, 1H), 7.52 (t, 1H), 7.57 (d, 1H), 7.71 (d, 1H), 7.82 (s, 1H), 11.16 (bs, 1H)
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