Triphenylphosphine → (R)-tert-butyl 2-((5-chloropyridin-3-yloxy)methyl)pyrrolidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 5-chloropyridin-3-ol (1.46 g, 11.28 mmol), (R)-tert-butyl 2-(hydroxymethyl)pyrrolidine-1-carboxylate (2.27 g, 11.28 mmol), and triphenylphosphine (2.96 g, 11.28 mmol) in THF (50 mL) was added di-tert-butyl azodicarboxylate (DTAD) (2.60 g, 11.28 mmol) at 0° C. The mixture was stirred at 0° C. for 1 h and warmed to room temperature. After being stirred at room temperature for 2 days, the mixture was concentrated in vacuo to afford a dark brown viscous oil. The residual oil was crystallized from isopropyl ether (IPE)-hexane, and formed precipitate was removed by filtration. The filtrate was concentrated in vacuo to afford a dark brown oil. The residual oil was purified by silica gel column chromatography (ethyl acetate/hexane 1:9 to 1:5) to afford crude 5.15 g (quant.) of the title compound as a colorless gel. The crude title compound was used for the next step without further purification.

Provenance & Evidence