[C:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)#[N:2].F[C:17]1[CH:22]=[C:21]([CH3:23])[CH:20]=[CH:19][N:18]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[C:1]([C:3]1([C:17]2[CH:22]=[C:21]([CH3:23])[CH:20]=[CH:19][N:18]=2)[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)#[N:2]A mixture of tert-butyl 4-cyanopiperidine-1-carboxylate (15.2 g, 72.3 mmol) and 2-fluoro-4-methylpyridine (9.64 g, 87.0 mmol) was dissolved in 361 mL of THF. The reaction was purged with a stream of nitrogen and cooled to −78° C. To this reaction was added 1.0 M sodium bis(trimethylsilyl)amide in THF (101 mL, 101 mmol), which was stirred for 1 hour. The reaction was warmed to ambient temperature, stirred for 36 hours, and quenched with a saturated ammonium chloride solution. The mixture was extracted with dichloromethane (3×200 mL). The combined organic extracts were dried over sodium sulfate, filtered, concentrated, and subjected to silica gel chromatography eluting with 0-25% EtOAc in hexanes to yield tert-butyl 4-cyano-4-(4-methylpyridin-2-yl)piperidine-1-carboxylate.
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