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 (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-PrSO2Cl (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-(propylsulfonyl)-4-pyridin-2-ylpiperidine-4-carbonitrile. 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-af49c2df54914753a1c661b8c2345761

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07834031B2