1,4-Dioxane hydrochloride → 5'-chloro-N-((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-2'-fluoro-2,4'-bipyridin-6-amine

To a solution of tert-butyl 5′-chloro-2′-fluoro-2,4′-bipyridin-6-yl((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)carbamate (950 mg, 2.111 mmol) in methanol (5 mL) was added 4M HCl/dioxane (15 mL, 494 mmol). The resulting mixture was stirred for ˜45 min at ambient temperature. The mixture then was concentrated in vacuo and the resulting residue was dissolved in EtOAc (˜50 mL) and saturated aqueous NaHCO3 solution (˜50 mL). The separated organic layer was washed with saturated aqueous NaHCO3 solution (1×), brine (1×), dried over Na2SO4, filtered off and concentrated in vacuo providing crude (R/S)-5′-chloro-N-((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)-2′-fluoro-2,4′-bipyridin-6-amine as a colorless oil, which was directly used in the next reaction without further purification. Yield: 740 mg. LCMS (m/z): 350.1 [M+H]+; Retention time=0.69 min.

1. concentrationThe mixture then was concentrated in vacuo
2. dissolutionthe resulting residue was dissolved in EtOAc (˜50 mL)
3. washThe separated organic layer was washed with saturated aqueous NaHCO3 solution (1×), brine (1×)
4. dry with materialdried over Na2SO4
5. filtrationfiltered off
6. concentrationconcentrated in vacuo

ORD record

ord-bc637f798a584a2b895646a9ba872df0

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08778951B2