[C:1]([CH2:3][C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5])#[N:2].C[Si](C)(C)N[Si](C)(C)C.[Li].Cl[C:22]1[N:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][N:23]=1>C1COCC1>[C:1]([C:3](=[C:22]1[N:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][NH:23]1)[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5])#[N:2]tert-Butyl 2-cyanoacetate (97.45 g, 690 mmol) was dissolved in anhydrous THF (1 L), and cooled on an ice-bath for 90 min with stirring under nitrogen. A 1M solution of lithium hexamethyldisilazane in THF (690 mL, 690 mmol) was added dropwise. The mixture was stirred for an additional 1 hr, then 2-chloro-4-trifluoromethylpyrimidin (105 g, 590 mmol) was added dropwise. The mixture was then heated to 50° C. for 3 hr with stirring under nitrogen, allowed to cool, and the solvent removed under reduced pressure. Hydrochloric acid (1N) was added to the residue to achieve a pH of 1-2. The precipitated solids were collected by filtration and dried under vacuum to give tert-butyl 2-cyano-2-[4-trifluoromethylpyrimidin-2(1H)-ylidene]acetate (135 g, 82% yield) as a bright yellow solid, >98% pure by LC/MS. tert-Butyl 2-cyano-2-[4-trifluoromethylpyrimidin-2(1H)-ylidene]acetate (48 g; 166 mmol) was suspended in 4M hydrogen chloride in dioxane (415 mL, 1.66 mol) and the mixture stirred at room temperature for 6 hr, then concentrated under reduced pressure to give 2-(4-trifluoromethylpyrimidin-2-yl)acetonitrile (31 g, 100% yield) as an orange oil, >98% pure by LC/MS. To a stirred solution of 2-(4-trifluoromethylpyrimidin-2-yl)acetonitrile (31.0 g; 166 mmol) in absolute ethanol (800 mL) was added potassium O-ethylxanthate (26.6 g; 166 mmol) followed by potassium carbonate (45.8 g; 332 mmol). The mixture was heated to 100° C. for 3 hr, cooled to room temperature, iodomethane (47.1 g; 332 mmol) added dropwise, and 1N hydrochloric acid (2 L) added. The resulting mixture was extracted with DCM (1.5 L), and the DCM layer was washed twice with brine (1 L each). The solvent was removed under reduced pressure to give 3,3-bis(methylthio)-2-(4-trifluoromethylpyrimidin-2-yl)acrylonitrile (36 g, 75% yield) as a light brown solid, >95% pure by LC/MS.
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