N,N'-Dimethylethylenediamine → 1-(4-Amino-2-chlorophenyl)-3-({[tert-butyl(diphenyl)silyl]oxy}methyl)piperidin-2-one

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Reaction Steps

2.75 g (10.8 mmol) of 3-chloro-4-iodoaniline are dissolved in 20 ml of anhydrous dioxane and admixed successively with 4.98 g (13.5 mmol) of the compound from example 92A, 103 mg (0542 mmol) of copper(I) iodide, 4.61 g (21.7 mmol) of potassium phosphate and 116 μl (1.085 mmol) of N,N′-dimethylethylenediamine. The reflux apparatus is inertized by repeated application of a gentle vacuum and flushing with argon. The reaction mixture is heated to reflux for 15 hours. After this time, it is allowed to cool to RT. It is admixed with water and extracted with ethyl acetate. The organic extract is washed successively with water and saturated sodium chloride solution. Then it is dried over anhydrous magnesium sulfate and filtered, and the filtrate is freed of the solvent under reduced pressure. The crude product thus obtained is first purified by suction filtration through silica gel with 20:1→1:4 cyclohexane/ethyl acetate as the eluent. This affords 3.12 g of a still-contaminated product which is purified further by means of preparative HPLC with an acetonitrile/water mixture. This affords 0.71 g (13% of theory) of the title compound.

Provenance & Evidence