[C:1]([O:5][C:6](=[O:17])[CH:7]([C:10]1[CH:15]=[CH:14][C:13](Br)=[CH:12][N:11]=1)[C:8]#[N:9])([CH3:4])([CH3:3])[CH3:2].[CH2:18]([Zn]CC)[CH3:19].[Cl-].[NH4+].CCOC(C)=O>C1COCC1.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C(Cl)Cl>[C:1]([O:5][C:6](=[O:17])[CH:7]([C:8]#[N:9])[C:10]1[CH:15]=[CH:14][C:13]([CH2:18][CH3:19])=[CH:12][N:11]=1)([CH3:4])([CH3:3])[CH3:2]The crude (5-bromo-pyridin-2-yl)-cyano-acetic acid tert-butyl ester (20.1 g) was dissolved in anhydrous THF (300 mL) and the dark red solution was cooled in an ice-water bath. After purging in a stream of nitrogen, diethylzinc (88.0 mL, 88.0 mmol, 1M in hexane) was slowly added over 50 minutes. The internal temperature was maintained below 4° C. The catalyst 1,1′-bis(diphenylphosphino)ferrocene palladium dichloride-CH2Cl2 (1:1 complex) (1.61 g, 1.97 mmol) was added and the mixture was heated at 50° C. for 35 minutes. The reaction was cooled in an ice bath and saturated aqueous ammonium chloride solution was added. The mixture was stirred for 10 minutes and EtOAc was added. The mixture was filtered through Celite® with the aid of EtOAc. The filtrate layers were separated and the organic layer was washed with brine and was dried over anhydrous sodium sulfate. The organic solution was concentrated to dryness and the residue was purified by ISCO (Teledyne Isco Inc., Lincoln) column chromatography (EtOAc/heptanes gradient) to give cyano-(5-ethyl-pyridin-2-yl)-acetic acid tert-butyl ester as a dark yellow solid (7.31 g). This material was used directly in the next step.
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