Uses
Used in the coupling reaction in Iron-and Cobalt-Catalyzed Arylation of Azetidines, Pyrrolidines, and Piperidines with Grignard Reagents.
Synthesis
The general procedure for the synthesis of N-Boc-4-iodopiperidine from N-Boc-4-hydroxypiperidine was as follows: to a solution of N-Boc-4-hydroxypiperidine (10.0 g, 49.7 mmol) in dichloromethane (200 mL) was added triphenylphosphine (16.9 g, 64.6 mmol) and imidazole (5.07 g, 74.5 mmol) sequentially. After the reaction mixture was cooled to 0°C in an ice bath, iodine (15.1 g, 59.6 mmol) was added slowly in portions. After addition, the reaction mixture was stirred at room temperature for 18 hours. After completion of the reaction, the reaction solution was diluted with water and extracted with ether. The organic layers were combined, washed sequentially with water and saturated sodium chloride solution and dried over anhydrous sodium sulfate. The solvent was removed by concentration under reduced pressure and the residue was ground with hexane to remove excess triphenylphosphine and triphenylphosphine oxide. After filtration, the filtrate was concentrated under reduced pressure to afford the target product N-Boc-4-iodopiperidine as a colorless oil (14.4 g, 93% yield).
References
[1] Patent: US2005/9838, 2005, A1. Location in patent: Page 143
[2] Patent: WO2018/106636, 2018, A1. Location in patent: Paragraph 00283
[3] Patent: WO2011/143366, 2011, A1. Location in patent: Page/Page column 45
[4] Journal of Organic Chemistry, 2004, vol. 69, # 15, p. 5120 - 5123
[5] Synlett, 1998, # 4, p. 379 - 380
