2-Fluoro-3-iodopyrazine → Tert-butyl 3-(3-fluoropyrazin-2-yl)pyrrolidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

Into an oven-dried flask were charged 2-fluoro-3-iodopyrazine (3.08 g, 13.8 mmol), 1,1′-bis(diphenylphosphino)ferrocene]dichloride palladium(ii)complex with dichloramethane (0.34 g, 0.41 mmol), copper(i) iodide (0.16 g, 0.83 mmol), and DMA (20 mL). The resulting mixture was degassed with alternating vacuum/nitrogen purges. The (1-(tert-butoxycarbonyl)pyrrolidin-3-yl)zinc(II) iodide (6.98 g, 19.3 mmol) solution from previous step was filtered through a regular filter into the mixture. It was degassed one more time and then heated to 80° C. with stirring for 16 h. After cooling to RT, the reaction mixture was partitioned between EtOAc and 1 N NH4Cl. The aqueous layer was back extracted with EtOAc (2×) and the combined EtOAc layers were washed once again with 1 N NH4Cl, then with brine, dried (Na2SO4) and concentrated. The crude material as chromatographed through a Redi-Sep pre-packed silica gel column (120 g), eluting with a gradient of 0% to 30% EtOAc in hexane, to provide tert-butyl 3-(3-fluoropyrazin-2-yl)pyrrolidine-1-carboxylate as orange oil. MS (ESI, pos. ion) m/z: 212.0 (M−56).

Provenance & Evidence