C[Li].[CH3:3]C1(C)CCCC(C)(C)N1.[CH2:13]([O:15][C:16]1[C:17]([F:27])=[C:18]([CH:21]=[CH:22][C:23]=1[O:24][CH2:25][CH3:26])[C:19]#[N:20])[CH3:14].CI.Cl>O1CCCC1>[CH2:13]([O:15][C:16]1[C:17]([F:27])=[C:18]([C:21]([CH3:3])=[CH:22][C:23]=1[O:24][CH2:25][CH3:26])[C:19]#[N:20])[CH3:14]Under a stream of nitrogen gas, methyl lithium (1.03 M diethyl ether solution, 18.2 mL, 18.8 mmol) was added to an ice-cooled solution of 2,2,6,6-tetramethylpiperidine (3.16 mL, 18.7 mmol) in tetrahydrofuran (30 mL), followed by 30 minutes of stirring. After cooling the reaction system to −78° C., a solution of 3,4-diethoxy-2-fluorobenzonitrile (3.90 g, 18.6 mmol) in tetrahydrofuran (20 mL) was added dropwise, and 30 minutes later, methyl iodide (1.4 mL, 22.4 mmol) was added dropwise, followed by 2 hours of stirring. The reaction system was gradually warmed to room temperature, and 1N hydrochloric acid was added to the reaction solution, after which ethyl acetate extraction was performed. The extract was washed with water and saturated brine, and then dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off, and the residue was purified by silica gel column chromatography (n-hexane, ethyl acetate) to give 3.40 g of the subject compound (yield: 81.7%).
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