C(NC(C)C)(C)C.C([Li])CCC.[Si:13]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].[F:28][C:29]1[CH:40]=[CH:39][C:32]([C:33](N(OC)C)=[O:34])=[CH:31][CH:30]=1.[Cl-].[NH4+]>C1COCC1.O>[F:28][C:29]1[CH:40]=[CH:39][C:32]([C:33]([CH:21]([C:22]2[CH:23]=[CH:24][N:25]=[CH:26][CH:27]=2)[O:20][Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14])=[O:34])=[CH:31][CH:30]=1Into a 2 L 3-necked round bottom flask fitted with a thermometer, dry nitrogen gas inlet, addition funnel and mechanical stirrer was added diisopropylamine (65 mL, 0.46 mol) in THF (120 mL). Cooled to -20° C. with a isopropyl alcohol/dry ice bath and added a solution of n-butyllithium in hexanes (210 mL of a 2.5M solution, 0.53 mol). Stirred at -15° C. for 30 min, then cooled to -20° C. Added 4-t-butydimethylsilyloxymethylpyridine from Step A (98.2 g, 0.44 mol) neat over a 30 min period. Let stir for 45 min at -20° C. To this mixture was added a solution of 4-fluoro-N-methoxy-N-methyl-benzamide (84.5 g, 0.46 mol) in THF (90 mL) over a 30 min period. The dark solution was stirred at 0° C. for 1 h, then warmed slowly to room temperature for 30 min. The reaction was poured into water (500 mL) containing ammonium chloride (100 g). After stirring for 10 min at room temperature, the solution was extracted with ethyl acetate (3 times). The combined organic extracts were washed successively with water and saturated salt solution. The combined aqueous layers were extracted with ethyl acetate. The combined ethyl acetate extracts were dried over anhydrous magnesium sulfate. The solution was filtered and the solvent removed by rotoevaporation. The residue was purified by flash column chromatography on silica gel eluted with 15-50% ethyl acetate in hexanes (17 L in total). The solvent was removed by rotoevaporation to yield the tide compound as an amber oil (120.4 g, 74% yield).
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