Dimethylamine → benzyl 4-[(1R,2S)-2-(2-{4-[2-(dimethylamino)-2-oxoethyl]-2,5-difluorophenoxy}ethyl)cyclopropyl]piperidine-1-carboxylate

To a solution of {4-[2-((1S,2R)-2-{1-[(benzyloxy)carbonyl]piperidin-4-yl}cyclopropyl)ethoxy]-2,5-difluorophenyl}acetic acid (313 mg, 0.661 mmol) in 2.5 ml anhydrous DMF at RT was added dimethylamine, 2.0 M solution in THF (0.661 ml, 1.32 mmol) and N,N-diisopropylethylamine (0.562 ml, 3.31 mmol). O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (503 mg, 1.32 mmol) was added into the solution and stirred at RT overnight. The reaction mixture in 12 ml water was extracted with 12 ml ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified on Biotage column (25 g silica gel) using a gradient eluent of 0-50% ethyl acetate in hexanes (800 ml) to afford the title compound. LC/MS (m/z): 501.4 (M+H)+.

1. extractionThe reaction mixture in 12 ml water was extracted with 12 ml ethyl acetate
2. dry with materialThe organic layer was dried over sodium sulfate
3. filtrationfiltered
4. concentrationthe filtrate was concentrated under reduced pressure
5. customThe residue was purified on Biotage column (25 g silica gel)

ORD record

ord-f95576435a11402e9bcf5afde702fb64

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08957062B2