Tert-butyl 4-cyano-4-(pyridin-2-YL)piperidine-1-carboxylate → 4-(Pyridin-2-yl)piperidine-4-carbonitrile

tert-Butyl 4-cyano-4-pyridin-2-ylpiperidine-1-carboxylate (I-2, 5.45 g, 19 mmol) was dissolved in TFA/CH2Cl2 (1:1, 50 mL) at 0° C. After stirring 40 min, the reaction mixture was concentrated under reduced pressure. The residue was diluted with 2 N NaOH in saturated aqueous NaCl (1:1, 80 mL) and extracted with EtOAc (5×200 mL). The combined extracts were washed with saturated aqueous NaCl, dried (MgSO4), and concentrated under reduced pressure to afford 4-pyridin-2-ylpiperidine-4-carbonitrile (3.55 g, 19 mmol) which was used immediately in subsequent reactions. A solution of 4-pyridin-2-ylpiperidine-4-carbonitrile (3.55 g, 19 mmol) in CH2Cl2 (50 mL) at 0° C. was treated with i-Pr2NEt (10 mL) and n-EtSO2Cl (2,24 mL, 21 mmol). After stirring for 1 h at 0° C., the reaction mixture was treated with 2 N NaOH and stirred vigorously for an additional 1 h, before being extracted with EtOAc (4×200 mL). The combined organic extracts were washed with saturated aqueous NaCl, dried (MgSO4), and concentrated under reduced pressure to afford 1-ethylsulfonyl)-4-pyridin-2-ylpiperidine-4-carbonitrile (I-3) as a yellow-brown solid. Analytical LCMS: single peak (214 nm), 1.6501 min. This material was used in subsequent reactions without further purification.

1. concentrationthe reaction mixture was concentrated under reduced pressure
2. additionThe residue was diluted with 2 N NaOH in saturated aqueous NaCl (1:1, 80 mL)
3. extractionextracted with EtOAc (5×200 mL)
4. washThe combined extracts were washed with saturated aqueous NaCl
5. dry with materialdried (MgSO4)
6. concentrationconcentrated under reduced pressure

ORD record

ord-e13c26b4fd184980b87272086759cf70

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07825135B2