[F:1][C:2]1[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=1[CH2:4][N:5]1[CH2:12][CH2:11][C:8]2([O:10][CH2:9]2)[CH2:7][CH2:6]1.[OH:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=1.C(=O)([O-])[O-].[K+].[K+].Cl.CCO>C(O)C.C(OCC)(=O)C.CN(C)C=O>[F:1][C:2]1[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=1[CH2:4][N:5]1[CH2:12][CH2:11][C:8]([CH2:9][N:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]2=[O:17])([OH:10])[CH2:7][CH2:6]1
23.00 g (0.104 mol) of N-(2-fluorobenzyl)-1-oxa-6-azaspiro[2,5]-octane and 10.30 g (0.108 mol) of 2-hydroxy-pyridine were weighed and added into 80 mL N,N-dimethylformamide, and then 1.00 g (0.007 mol) potassium carbonate was added. The reaction was stirred and reacted at a bath temperature of about 80° C. for 1 day, and the solvent was recovered. Potassium carbonate aqueous solution was added into the residue The mixture was extracted with dichloromethane twice, combined, washed with water, and dried. The solvent was recovered, crystallized with petroleum ether-ethyl acetate to obtain colorless flake-like crystal, 22.80 g, yield 69.3%. 1H-NMR (CDCl3, ppm) δ: 7.372 (2H, m), 7.228 (2H, m), 7.092 (1H, t, J=7.56 Hz), 7.020 (1H, t, J=8.96 9.24 Hz), 6.639 (1H, d, J=9.24 Hz), 6.228 (1H, t×d, J1=6.72 Hz, J2=1.12 Hz), 4.720 (1H, s), 4.036 (2H, s), 3.603 (2H, s), 2.69 (2H, dd, J1=7.84 Hz, J2=3.64 Hz), 2.46 (2H, t×d, J1=8.40 Hz, J2=2.80 Hz), 1.55-1.74 (4H, m). The product was heated and dissolved in ethanol-ethyl acetate, salified with HCl-EtOH while warm and naturally cooled to obtain a colorless fine granular crystal, which was dried under vacuum to obtain 20.00 g product. Melting point: 249-251° C.
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