Synthesis
General procedure for the synthesis of 4-(Boc-amino)-3-iodopyridine from 4-(tert-butoxycarbonylamino)pyridine: n-butyllithium (1.6 M hexane solution, 220 ml, 0.35 mol) was added slowly and dropwise over a period of 30 min to a stirred solution of 4-(tert-butoxycarbonylamino)pyridine (26.08 g, 0.13 mol) and N,N,N' ,N'-tetramethylethylenediamine (55 ml, 0.36 mol) in a solution of tetrahydrofuran (750 ml). The reaction mixture was stirred at -78°C for 15 minutes, followed by warming to -10°C and continued stirring for 2 hours. The reaction mixture was re-cooled to -78°C and a solution of iodine (95.11 g, 0.37 mol) in tetrahydrofuran (250 ml) was added dropwise over 30 minutes. After the dropwise addition, the mixture was continued to be stirred at -78°C for 2 hours. Upon completion of the reaction, the reaction mixture was cooled to 0°C using an ice water bath and the reaction was quenched by the slow addition of water (250 ml). Saturated sodium sulfite solution (100 ml) was then added and the organic layer was separated. The aqueous layer was extracted with dichloromethane (2 x 500 ml), the organic layers were combined, dried with anhydrous sodium sulfate and concentrated under reduced pressure to give a brown oil. The crude product was purified by silica gel fast column chromatography with 20% ethyl acetate/heptane as eluent to afford tert-butyl (3-iodopyridin-4-yl)-carbamate (25.00 g, 58%) as an off-white solid.1H NMR (400 MHz, CDCl3) δ 8.76 (1H, s), 8.35 (1H, d, J = 5.7 Hz), 8.11 (1H , d, J = 5.7 Hz), 7.04 (1H, br s), 1.55 (9H, s); retention time (Tr) = 0.99 min, m/z (ES+) (M+H)+ 321.08.
References
[1] Patent: WO2005/121141, 2005, A1. Location in patent: Page/Page column 13; 20
[2] Journal of Organic Chemistry, 2004, vol. 69, # 20, p. 6772 - 6780
