Hydrochloric Acid → (2S)-2-(4-([1,2,4]oxadiazol-3-yl)phenyl)piperazine dihydrochloride

Hydroxylamine hydrochloride (1.3 g, 20.2 mmol) and sodium carbonate (3.4 g, 32.1 mmol) were added to a solution of di-tert-butyl (2S)-2-(4-cyanophenyl)piperazine-1,4-dicarboxylate (2.5 g, 6.45 mmol) in ethanol (15 ml) and water (15 ml) at the room temperature and the solution was stirred at 80° C. for 2 hours. The mixture was partitioned between water and chloroform. The organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuo. Triethyl orthoformate (9.6 g, 64.8 mmol) and p-toluenesulfonic acid monohydrate (0.12 g, 0.63 mmol) were added to a solution of the residue in toluene (25 ml) and stirred at 90° C. for 2 hours. The mixture was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting 10-20% ethyl acetate in hexane to furnish di-tert-butyl (2S)-2-(4-([1,2,4]oxadiazol-3-yl)phenyl)-piperazine-1,4-dicarboxylate (1.94 g, 70%) as a colorless oil. Hydrogen chloride in ethyl acetate (4N) was added to a solution of di-tert-butyl (2S)-2-(4-([1,2,4]oxadiazol-3-yl)phenyl)piperazine-1,4-dicarboxylate (1.94 g, 4.51 mmol) in methanol and the mixture was stirred at room temperature for one hour. The solvent was evaporated under reduced pressure to give white solid, which was washed with ethyl acetate to afford (2S)-2-(4-([1,2,4]oxadiazol-3-yl)phenyl)piperazine dihydrochloride (1.3 g, 95%) as white crystals.

1. customThe solvent was evaporated under reduced pressure
2. customto give white solid, which
3. washwas washed with ethyl acetate

ORD record

ord-96c1a4b3f1bc41c794a005d396a01fcf

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08129377B2