Br[C:2]1[C:3]([F:8])=[N:4][CH:5]=[CH:6][CH:7]=1.[I-].[C:10]([O:14][C:15]([N:17]1[CH2:21][CH2:20][CH:19]([Zn+])[CH2:18]1)=[O:16])([CH3:13])([CH3:12])[CH3:11]>[Pd].[Cu]I.CC(N(C)C)=O>[F:8][C:3]1[C:2]([CH:20]2[CH2:19][CH2:18][N:17]([C:15]([O:14][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:16])[CH2:21]2)=[CH:7][CH:6]=[CH:5][N:4]=1
Into an oven-dried flask were charged 3-bromo-2-fluoropyridine (1.3 g, 7.39 mmol), Pd catalyst (0.181 g, 0.222 mmol), copper(i) iodide (0.084 g, 0.443 mmol), and DMA (10 mL). The resulting mixture was degassed with alternating vacuum/nitrogen purges. The (1-(tert-butoxycarbonyl)pyrrolidin-3-yl)zinc(II) iodide (3.75 g, 10.34 mmol) solution from previous step was filtered 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 layer was washed once again with 1 N NH4Cl, then with brine, dried (Na2SO4) and concentrated. The crude material as chromatography through a Redi-Sep pre-packed silica gel column (120 g), eluting with a gradient of 0% to 40% EtOAc in hexane, to provide tert-butyl 3-(2-fluoropyridin-3-yl)pyrrolidine-1-carboxylate as dark-red oil. [M−56]=211.2.
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