Methyl morpholine oxide → N-[4-cyano-3-(trifluoromethyl)phenyl]-2,3-dihydroxy-2-methylpropanamide

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Reaction Steps

In a 50 ml flask, equipped with a magnetic stirrer, 0.50 g of the compound (7) in 1.8 ml of tert-butyl alcohol was added to a mixture of 0.301 g of N-methylmorpholine-N-oxide (=NMO) (monohydrate) and 16 mg of osmium tetroxide in 15 ml of a water/acetone mixture (5:2). The reaction mixture was stirred at room temperature overnight. The conversion was ˜60%. Another 0.30 g of NMO (monohydrate) and 16 mg of osmium tetroxide were added and the reaction was followed with HPLC. Stirring was continued for 3.5 hours. The reaction was worked-up by addition of a slurry of 1.0 g NaHSO3 and 1.0 g of Celite in 40 ml of water. The Celite was removed by filtration, and the filtrate was neutralised to pH 7.0 with 1N aqueous H2SO4, and the acetone was removed at reduced pressure. The remaining solution was set to pH 2.0 with 1N aqueous H2SO4 and was extracted with 3×35 ml of ethyl acetate. The combined organic layers were washed with 35 ml of brine, dried (Na2SO4) and concentrated at reduced pressure. The crude product was purified by column chromatography (Merck 60 SiO2, eluens ethyl acetate) to give the purified (5C) as a slightly coloured oil, which solidified (off-white solid) after a few days. Isolated yield: 0.400 gram (70.5%). 1H-NMR confirmed the structure.

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