Ethyl 4-piperidinecarboxylate → Ethyl 1-(2,2,2-trifluoro-1-(3-(trifluoromethyl)phenyl)ethyl)piperidine-4-carboxylate

To a solution of 0.355 ml of 2,2,2-trifluoro-1-(3-(trifluoromethyl)phenyl)ethanone in 12 ml of dichloromethane were added 0.32 ml of ethyl isonipecotate, 0.58 ml of triethylamine and 1.05 ml of a toluene solution containing 1 M titanium(IV) chloride at room temperature, followed by stirring the reaction mixture at room temperature overnight. To the reaction mixture was added a solution of 392 mg of sodium cyanoborohydride in 5 ml of methanol at room temperature, followed by stirring the reaction mixture at room temperature for 6 hours. Ethyl acetate and saturated aqueous sodium bicarbonate solution were added to the reaction mixture. An insoluble matter was filtered off using Celite. The ethyl acetate layer was separated, washed with brine, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated in vacuo. The resulting residue was purified by a silica gel column chromatography (eluent: hexane to hexane/ethyl acetate=4/1) to give the title compound as a yellow oil.

1. stirringby stirring the reaction mixture at room temperature for 6 hours
2. filtrationAn insoluble matter was filtered off
3. customThe ethyl acetate layer was separated
4. washwashed with brine
5. dry with materialdried over anhydrous magnesium sulfate
6. filtrationfiltered
7. concentrationThe filtrate was concentrated in vacuo
8. customThe resulting residue was purified by a silica gel column chromatography (eluent: hexane to hexane/ethyl acetate=4/1)

ORD record

ord-0d332d6174b84c70b4e2fbdbd85b866a

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08519136B2