Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[Li]CCCC.[O:14]1[C:18]2([CH2:23][CH2:22][C:21](=[O:24])[CH2:20][CH2:19]2)[O:17][CH2:16][CH2:15]1.C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1.C(Cl)Cl>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([C:21]2([OH:24])[CH2:22][CH2:23][C:18]3([O:17][CH2:16][CH2:15][O:14]3)[CH2:19][CH2:20]2)=[N:3][CH:4]=1
To a solution of 2,5-dibromopyridine (4.10 g, 17 mmol) in anhydrous toluene (250 mL) at −78° C. was dropwise added n-BuLi (1.6 M, 12 mL). After stirred at −78° C. for 2.5 hours, a solution of 1,4-dioxa-spiro[4.5]decan-8-one (2.73 g, 17 mmol) in methylene chloride (25 mL) was added into the reaction mixture, and the resulting mixture was stirred for additional one hour and allowed to warm up to rt slowly. The reaction mixture was poured into aqueous NaHCO3 (200 mL) and then extracted with EtOAc (2×50 mL). The organic extracts were combined, washed with saline solution (2×50 mL), dried over MgSO4, concentrated in vacuo. The resulting solid was titrated with ether and the filtrate was collected. The ether was removed and the solid was chromatographed on silica gel, eluting with hexane/ethyl acetate (2 to 1), to give 8-(5-bromopyridin-2-yl)-1,4-dioxaspiro[4.5]decan-8-ol (4.27 g) as pale yellow solid. LCMS: 316.10/314.10 (M+H+, 100%). 1H NMR: δ 8.6 (s, 1 H), 7.82 (d, 1 H), 7.38 (d, 1 H), 4.6 (s, 1 H), 4.0 (m, 4 H), 2.2 (m, 4 H), 1.7 (m, 4 H).
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