Chemical Properties
Colorless Liquid
Uses
4-Chlorobutanal Dimethyl Acetal 90% is a compound useful in organic synthesis and other chemical processes. It is used as an intermediate in the synthesis of aripiprazole, buspirone, and NAN-190 via reductive alkylation of piperazine derivatives with aldehydes
Synthesis
Preparation of 4-chlorobutanal dimethanol: 72 g (0.49 mol) of 4-chloro-1-acetoxy-1-butene was dissolved in 300 mL of anhydrous methanol, to which were added 240 g (7.5 mol) of methanol and 15 g of acidic ion exchange resin catalyst treated with macroporous resin 15. The mixture was stirred overnight under reflux conditions and the complete conversion of the E and Z isomers of 4-chloro-1-acetoxy-1-butene to a single high-boiling product, accompanied by a small number of side reactions, was confirmed by GC analysis. Upon completion of the reaction, the mixture was filtered to recover the catalyst and the filtrate was treated with 5 g of solid sodium bicarbonate. Excess methanol was removed by distillation under reduced pressure until the volume was reduced to about 50 mL. The liquid was decanted from the insoluble sodium bicarbonate and distilled through a 6-inch Vigro fractionating column at 25 mm Hg. A colorless fraction with a boiling range of 83-85 °C was collected to give 55.0 g of product (74.4% of the theoretical yield).NMR analysis confirmed the fraction as pure 4-chlorobutanal dimethyl acetal.
References
[1] Organic Preparations and Procedures International, 2004, vol. 36, # 5, p. 487 - 490
[2] Patent: US2004/192958, 2004, A1. Location in patent: Page 3
