109-54-6

colorless liquid

3-Chloro-1-(N,N-dimethyl)propylamine is a genotoxic impurity in drug samples of rizatriptan benzoate. Also, it is the side chain of Chlorpromazine and Amitriptyline.

General procedure for the synthesis of 3-chloro-1-(N,N-dimethyl)propylamine from N,N-dimethylaminopropyl chloride hydrochloride: flake solid NaOH (42.1 g, 1052.5 mmol, 1.0 eq.) was dissolved in 142.1 g of water, a process which is exothermic, and an aqueous NaOH solution was obtained and then cooled down to 30 °C. In a 500 mL two-neck flask, HCl (104 g, 658 mmol, 1.0 eq.) and the above aqueous NaOH solution were added, the temperature was raised to 45 °C and the reaction was started with continuous stirring for 2 hours. After completion of the reaction, the reaction solution was cooled to room temperature (30 °C). The organic layer was separated and collected to give 74.93 g of wet 3-chloro-1-(N,N-dimethyl)propylamine (CPA). The water content of the product was determined to be 2.755% and the yield was 91.07% (as anhydrous CPA).

[1] Patent: CN105294496, 2016, A. Location in patent: Paragraph 0128; 0129; 0130; 0131; 0132
[2] Patent: CN106810523, 2017, A. Location in patent: Paragraph 0021
[3] Patent: WO2007/54105, 2007, A2. Location in patent: Page/Page column 20
[4] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1985, p. 2033 - 2038
[5] Patent: WO2009/133052, 2009, A1. Location in patent: Page/Page column 42