Synthesis
The general procedure for synthesizing N-pivaloyl-p-chloroaniline from pivaloyl chloride and 4-chloroaniline was as follows: referring to Example 2, 4-chloroaniline (113 kg, 886 mol), deionized water (565 L), and sodium bicarbonate (89.3 kg, 1.2 eq.) were added to ethyl acetate (1695 L). Pivaloyl chloride (112 kg, 1.05 eq.) was slowly added dropwise at 15°C or lower. After the dropwise addition was completed, the reaction solution was stirred at about 25°C for 2 hours. Upon completion of the reaction, the organic and aqueous layers were separated. The organic layer was washed twice with deionized water (848 L x 2) and then concentrated under reduced pressure to about 600 L. To the concentrate was added ethylcyclohexane (848 L) and again concentrated under reduced pressure to about 600 L. The residue was cooled to about 5 °C and stirred for 1 h to promote crystallization. The precipitated crystals were collected by filtration and dried under reduced pressure to afford N-pivaloyl-p-chloroaniline (187 kg, 99.7% yield).
References
[1] Patent: WO2005/121133, 2005, A1. Location in patent: Page/Page column 30-31
[2] Patent: US2009/247766, 2009, A1. Location in patent: Page/Page column 27
[3] Patent: WO2015/118515, 2015, A1. Location in patent: Page/Page column 9
[4] Journal of Organic Chemistry, 1998, vol. 63, # 23, p. 8536 - 8543
[5] Patent: CN105801442, 2016, A. Location in patent: Paragraph 0006; 0018; 0022; 0026; 0030
