(3S)-pyrrolidin-3-ol → 6-Acetyl-3-((S)-3-hydroxy-pyrrolidin-1-yl)-pyridine-2-carbonitrile

Participants

Reaction Conditions

Reaction Steps

6-Acetyl-3-chloro-pyridine-2-carbonitrile (64) (1.80 g, 9.97 mmol) was dissolved in MeCN (19 mL). (S)-3-Pyrrolidinol (884 μL, 10.9 mmol) and TEA (4.16 mL, 29.8 mmol) were added and the mixture stirred at 100° C. in the microwave for 20 minutes. The solvent was evaporated in vacuo and the crude material dissolved in EtOAc (100 mL). The solution was washed with 1:1 saturated brine solution-H2O (100 mL), saturated brine solution (100 mL), then dried (MgSO4), filtered and the solvent evaporated in vacuo. The crude product was purified by flash chromatography (Biotage SP1, 50 g SNAP cartridge) eluting with 6:4 isohexane-EtOAc→8:2 EtOAc-isohexane to yield the title compound as a yellow solid (1.32 g, 64%); LCMS, Rt=2.04 min (MeOH-FA method), m/z 232 (MH+).

Provenance & Evidence