Synthesis
The general procedure for the synthesis of N-(3-iodopyridin-2-yl)palmitamide from 2-(tert-pentanoylamino)pyridine was as follows: 2-(tert-pentanoylamino)pyridine (6a, 500 g, 2.8 mol) was dissolved in tetrahydrofuran (6 L) and cooled to -78 °C. To this cold solution, n-butyllithium (2.5 M hexane solution, 2.25 L, 5.63 mol) was slowly added at room temperature, controlling the rate of addition so that the reaction temperature did not exceed -55 °C. After addition, the mixture was stirred for 1 hour to ensure that the metallization reaction was complete. Subsequently, a tetrahydrofuran (1 L) solution of iodine (782 g, 3.01 mol) was slowly added at a temperature not exceeding -65 °C. After addition, stirring of the reaction mixture was continued for 2 hours. After completion of the reaction, the reaction mixture was slowly poured into ice water (6 L). The organic layer was separated by diluting the mixture with ethyl acetate (6 L). The aqueous layer was extracted with ethyl acetate (4 L) and the organic phases were combined. The organic phase was washed sequentially with aqueous sodium thiosulfate (200 g/L, 3 × 4 L) and saturated aqueous sodium chloride (2 × 4 L). The organic layer was dried with sodium sulfate and concentrated under reduced pressure to remove the solvent to give the tan solid product 7a, which was pure enough to be used directly in the next reaction. Yield: 800 g, 94% yield.
References
[1] Patent: US2006/183758, 2006, A1. Location in patent: Page/Page column 8
[2] Synthesis, 2008, # 13, p. 2049 - 2054
[3] Chemistry - A European Journal, 2010, vol. 16, # 27, p. 7992 - 7995
[4] Journal of the Chemical Society, Perkin Transactions 1, 2000, # 24, p. 4245 - 4249
[5] Patent: US2009/156593, 2009, A1. Location in patent: Page/Page column 17
