[H-].[Na+].[C:3]([CH2:5][C:6](OC)=O)#[N:4].[Br:10][C:11]1[CH:18]=C[C:14]([C:15]#[N:16])=[C:13](F)[CH:12]=1.Cl>CS(C)=O.O>[Br:10][C:11]1[CH:18]=[CH:6][C:5]([C:3]#[N:4])=[C:13]([CH2:14][C:15]#[N:16])[CH:12]=1Sodium hydride (47.2 g, 1.18 mol) was suspended in 320 mL DMSO and cooled to 0° C. in an ice-water bath. The mixture became viscous as the DMSO began to freeze. Methyl cyanoacetate (104 mL, 1.18 mol) was added slowly causing a slight temperature increase and thus a more easily stirrable solution. The mixture was stirred for 30 minutes at room temperature. 4-Bromo-2-fluorobenzonitrile (118 g, 590 mmol) (commercially available from Acros Organics (Order Number 29049)) was added via cannula as a solution in 500 mL DMSO. The mixture was heated to an internal temperature of 90° C. The mixture was cooled and allowed to stand overnight. 1.2 L of water was added to the reaction mixture. The mixture was heated to an internal temperature of 104° C. over 3 hours. 2.3 L of water was added and the mixture was heated at reflux 16 hours. The mixture was cooled to 5° C. and 700 mL of 0.2N HCl was added. The mixture was allowed to stir at 5° C. for 30 minutes. The resulting precipitate was filtered, washed with water, and dried to provide the product (102 g, 78%). LCMS (API-ES) m/z: 223, 221 (M+H+).
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