Hydrochloric Acid → 3-(2,5-difluoro-4-(methylsulfonyl)phenoxy)-1,4'-bipiperidin-2-one HCl salt

温度

110 °C

To a solution of tert-butyl 3-(4-bromo-2,5-difluorophenoxy)-2-oxo-1,4′-bipiperidine-1′-carboxylate (710 mg, 1.45 mmol) in DMSO (4 mL) was added Cu(I) triflate benzene complex (73 mg, 0.145 mmol), sodium methanesulfinate (222 mg, 2.18 mmol) and trans-cyclohexane-1,2-diamine (66.3 mg, 0.580 mmol). The reaction was heated at 110° C. overnight. The reaction was cooled to ambient temperature and diluted with water (5 mL) and EtOAc (5 mL). The organic layer was separated and the aqueous washed with EtOAc (2×10 mL). The combined organic layers were dried with MgSO4 and concentrated. The crude residue was purified over silica gel (2:1 hexanes/EtOAc) to give a clear oil. This material was then dissolved in CH2Cl2 (10 mL) and excess 2 N HCl in ether (5 mL) added. The reaction was allowed to stir overnight and then concentrated under vacuum to give 3-(2,5-difluoro-4-(methylsulfonyl)phenoxy)-1,4′-bipiperidin-2-one HCl salt (238 mg, 89%) was an off white solid.

1. temperatureThe reaction was cooled to ambient temperature
2. customThe organic layer was separated
3. washthe aqueous washed with EtOAc (2×10 mL)
4. dry with materialThe combined organic layers were dried with MgSO4
5. concentrationconcentrated
6. customThe crude residue was purified over silica gel (2:1 hexanes/EtOAc)
7. customto give a clear oil
8. concentrationconcentrated under vacuum

ORDレコード

ord-3e8f7d66bf5d40a093e21aa1238f632a

出典データセット

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08754226B2