Methyl iodide → 2-(4-Methoxyphenyl)-2-methylpropan-1-amine

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Reaction Steps

To a solution of (4-methoxy-phenyl)-acetonitrile [5 g, 34 mmol] in THF (40 mL), is added a 1.5 M solution of lithium diisopropylamide in cyclohexane (36 mL, 54 mmol) at −78° C. After 2 hours at −78° C., methyl iodide (3.4 g, 54 mmol) is added, and the mixture is allowed to warm to room temperature over 3 hours. After additional 12 hours at 20° C., the mixture is diluted with aqueous ammonium chloride solution, and extracted with ethyl acetate. The extracts are dried over magnesium sulfate, filtered and concentrated. The residue is subjected to chromatography on silica gel eluting with 40% EtOAc in heptane to afford a mixture of 2-(4-ethoxy-phenyl)-propionitrile and 2-(4-methoxy-phenyl)-2-methyl-propionitrile. To above mixture (5 g) in THF (20 mL) is add a 2 M solution of lithium aluminum hydride (35 mL, 70 mmol) at 0° C. After 12 hours at 20° C., the mixture is carefully quenched with 10% sodium hydroxide solution, and the white slurry is diluted with ether. The mixture is dried over magnesium sulfate, filtered and concentrated. The residue is subjected to chromatography on silica to afford 2-(4-methoxy-phenyl)-2-methyl-propylamine [2 g, 33%, Intermediate (35)]. MS: 180 (M+H).

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