[O:1]1CCC[CH2:2]1.C([Mg]Cl)CCC.CCCCCC.C([Li])CCC.Br[C:24]1[CH:29]=[CH:28][C:27]([CH:30]([O:34][CH:35]2[CH2:40][CH2:39][CH2:38][CH2:37][O:36]2)[CH2:31][O:32][CH3:33])=[CH:26][N:25]=1.[Cl-].[NH4+]>O1CCCC1.CN(C)C=O>[CH3:33][O:32][CH2:31][CH:30]([C:27]1[CH:28]=[CH:29][C:24]([CH:2]=[O:1])=[N:25][CH:26]=1)[O:34][CH:35]1[CH2:40][CH2:39][CH2:38][CH2:37][O:36]1To tetrahydrofuran (250 mL) cooled to −20° C. were successively added a 2M butylmagnesium chloride tetrahydrofuran solution (11.2 mL) and a 1.6M n-butyllithium hexane solution (28.0 mL). The reaction mixture was stirred at −20° C. for 10 min, and a solution of 2-bromo-5-[2-methoxy-1-(tetrahydro-2H-pyran-2-yloxy)ethyl]pyridine (17.66 g) in tetrahydrofuran (15 mL) was added at −20° C. to −10° C. over 20 min. The reaction mixture was stirred at −10° C. for 30 min and N,N-dimethylformamide (8.2 g) was added. The reaction mixture was warmed to room temperature, saturated aqueous ammonium chloride solution was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The obtained residue was subjected to silica gel column chromatography, and the title compound (9.48 g, yield 64%) was obtained as a yellow oil from a fraction eluted with ethyl acetate-hexane (1:1, volume ratio). MS: 266 (MH+).
Loading…
