General procedure for the synthesis of N-(4-chlorobenzyl)-N-methylamine from 4-chlorobenzyl chloride and monomethylamine: an aqueous solution of methylamine (40% v/v, 9.03 ml, 93.48 mmol) was slowly added to a stirred tetrahydrofuran (THF, 300 ml) solution of 4-chlorobenzyl chloride (3.00 g, 18.63 mmol) under nitrogen protection and at 0 °C. The reaction mixture was stirred at room temperature overnight. Upon completion of the reaction, the solvent was removed by rotary evaporation and residual water was removed by azeotropy with toluene. The crude product was purified directly by column chromatography, first using ethyl acetate (100%) as eluent, followed by a solvent mixture of ethyl acetate: methanol: triethylamine (92:5:3) as eluent, to afford the target compound, N-(4-chlorobenzyl)-N-methylamine (30), as a yellow oil (2.49 g, 81% yield). The structure of the product was determined by NMR hydrogen spectrum (1H NMR, CDCl3, 300 MHz) δ 7.25-7.18 (4H, m), 3.66 (2H, s), 2.38 (3H, s), 1.65 (1H, s); NMR carbon spectrum (13C NMR, CDCl3, 100 MHz) δ 138.6, 132.6, 129.5 (2C ), 128.4 (2C), 55.2, 35.8; high-resolution mass spectrometry (HRMS, ESI): measured value 156.0580 (M+), theoretical value of 156.0556 for C8H10NCl (M+).
