Synthesis
General procedure for the synthesis of 4-(4-chlorophenyl)butyric acid from 3-(4-chlorobenzoyl)propionic acid: A mixture of 4-(4-chlorophenyl)-4-oxobutanoic acid (1 eq.), potassium hydroxide (KOH, 3 eq.), and hydrazine hydrate (2.2 eq.) in ethylene glycol was placed in a reaction flask and azeotropically refluxed for 5 hr at 120-130 °C. Subsequently, the reaction temperature was gradually increased to 180 °C and the reflux was continued at 190 °C for 3 hours. After completion of the reaction, the reaction mixture was cooled to 25 °C, diluted with water and poured into 2.5 N hydrochloric acid (HCl) solution for acidification, and white crystals were precipitated to give 4-(4-chlorophenyl)butyric acid in 89% yield.
References
[1] Patent: US6410585, 2002, B1
[2] Journal of Medicinal Chemistry, 1982, vol. 25, # 8, p. 947 - 952
[3] Patent: US2005/165004, 2005, A1. Location in patent: Page/Page column 28
[4] Patent: WO2015/134973, 2015, A1. Location in patent: Page/Page column 97; 98
[5] Angewandte Chemie - International Edition, 2017, vol. 56, # 41, p. 12476 - 12480
