An easy method and two steps for synthesis of the medetomidine with high yield

A two step method (consisting of transformation of aldehyde to alcohol and addition of imidazole group) was used for the synthesis of naphtalenic derivative of medetomidine and the optimized conditions were then applied to the synthesis of medetomidine. Thus, after optimization of first step (preparation of chiral alcohol), the various reaction parameters that affect the yield of naphtalenic derivative of medetomidine following second step were determined. then produced alcohol was treated by TMS-imidazole in the presence titanium tetrachloride in anhydrous chloroform and the reaction mixture is worked up of by two step addition of sodium hydroxide. The same conditions applied in the synthesis of medetomidine has afforded the same result (99% yield). NMR spectra were obtained on a Bruker DPX-250 instrument (250 MHz for 1H and 62.5 MHz for 13C), and CDCl3 and DMSO-d6 were used as solvents; chemical shifts are reported in (ppm) from TMS for 13C and 1H. Gas chromatogram (GC) spectra were recorded on Varian (STAR 3400CX) spectrometer with a packed column (10% OV-101 CWHP 80/100, 2m x 1.8”) and a He flow rate of 10 ml/min. Electronic ionization GC-MS spectra were recorded on a Varian (SATURN 4D) spectrometer using an ionization current of 8 A with a capillary column (DB-5MS, 0.1 micron, 30 m x 0.250 mm). Only m/z values having intensities of more than 10% are given, and retention times are reported with a He flow rate of 10 ml/min. HPLC analyses were performed on a Knauer EA 4300F equipped with a UV detector (215 nm), model 2600, and a C18 column (250 x 4.6 mm) with an eluent (H2O/EtOH, 25:75) flow rate of 1 mL/min. Melting points were obtained on a Mettler FP61 apparatus.