Synthesis
The general procedure for the synthesis of piperidinyl piperidine carbonyl chloride from 4-piperidinyl piperidine and triphosgene is as follows: Example 1 Synthesis of [1,4']bipiperidine-1'-carbonyl chloride (II): triphosgene (16.48 g) was dissolved in methylene chloride (200 ml), and methylene chloride solution of 4-piperidinyl piperidine (20 g) (200 ml) was slowly added, and the temperature of the reaction was maintained at 20 to 25 °C and the reaction time was 1-2 hours. During this process, dichloromethane was removed by distillation and acetonitrile was added subsequently. Distillation was continued to remove dichloromethane and acetonitrile until the reaction temperature was raised to 70°C. Fresh dichloromethane was added to the reaction mixture and after forming a homogeneous slurry, potassium carbonate (30-35 g) was added and the reaction mixture was stirred for 1-2 hours. After completion of the reaction, the reaction mixture was filtered and the filtrate was concentrated. Hexane was slowly added to the concentrate under stirring to precipitate a solid product. The solid was collected by filtration, washed with hexane and dried under reduced pressure at about 40 °C to give 27 g of product (98.5% yield). The product was analyzed by GC showing a purity of 99.80% and no dimer impurities were detected.
References
[1] Patent: US2011/144342, 2011, A1. Location in patent: Page/Page column 7
[2] Patent: EP2341046, 2011, A2. Location in patent: Page/Page column 9
[3] Patent: US2007/208050, 2007, A1. Location in patent: Page/Page column 7
[4] Patent: WO2009/97695, 2009, A1. Location in patent: Page/Page column 114-115
[5] Patent: WO2006/16203, 2006, A1. Location in patent: Page/Page column 8-9
