2-(3-fluorophenyl)-2-methylpropanenitrile synthesis

Yield:93748-10-8 93%

Reaction Conditions:

Stage #1: 3-fluorophenylacetonitrilewith lithium hexamethyldisilazane in tetrahydrofuran at -70 - -50; for 1 h;Inert atmosphere;
Stage #2: methyl iodide in tetrahydrofuran at -50 - 20;

Steps:

73.1

Step 1: 2-(3-fluoro-phenyl)-2-methyl-propionitrile Under an argon atmosphere 77 mL (77 mmol) of a 1M lithium bis(trimethylsilyl)amide solution was added dropwise at -70° C. to 5.0 g (37 mmol) (3-fluoro-phenyl)-acetonitrile in 150 mL THF. The mixture was allowed to come up to -50° C. and was then stirred at this temperature for 1 h. Then at -50° C. 4.8 mL (78 mmol) methyl iodide were added. The reaction mixture was heated to RT overnight. The reaction mixture was slowly combined with saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic phase was dried on sodium sulphate and evaporated down. Yield: 5.6 g (93% of theory) ESI-MS: m/z=163 (M+H)⁺

References:

US2011/195954,2011,A1 Location in patent:Page/Page column 107