Citric Acid → (R)-5-(6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl)-N-methyl-1,2,4-oxadiazole-3-carboxamide

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Reaction Steps

A solution of (3R)-6-cyclohexyl-3-{3-[(methylamino)carbonyl]-1,2,4-oxadiazol-5-yl}hexanoic acid (Preparation 8) (285 mg, 0.88 mmol) and N-methylmorpholine (110 μl, 1.00 mmol) in anhydrous tetrahydrofuran (10 ml) was cooled to 0° C., treated with isobutyl chloroformate (130 μl, 1.00 mmol) and stirred under a nitrogen atmosphere for 1 hour. O-(Trimethylsilyl)hydroxylamine (130 μl, 1.06 mmol) was added and the mixture was stirred for 18 hours, being allowed to warm to room temperature over this time. The mixture was then treated with aqueous citric acid solution (10% w/v, 10 ml) and stirred for 2 hours. This mixture was diluted with water and extracted with ethyl acetate (×3). The combined organic layers were washed sequentially with water and brine, dried over anhydrous sodium sulphate, filtered and the solvent removed under reduced pressure. The solid was then recrystallised from hexane:ethyl acetate to afford the title compound as a white solid (130 mg).

Provenance & Evidence