From WikiSynth
The 28.04 g (107 millimoles) of oil remaining from Example 1 was converted to the hydrochloride by standard methods, e.g., as in U.S. Pat. No. 3,652,589. The product was air dried to give 28.7 g of the hydrochloride as a white solid (89% for this step). HPLC indicated a 91/9 ratio of trans/cis. Of this, 28.53 g was recrystallized from 255 mL acetonitrile (8.5-9 mL per g of compound) with mechanical stirring (also on cooling) to give 18.8 g. A second recrystallization from 170 mL of acetonitrile gave 16.49 g. The final recrystallization from 62 mL isopropanol (use about 3.8 mL/g of compound) gave 13.39 g. HPLC indicated a 99.99/0.01 ratio of trans/cis. It is seen that recrystallization from acetonitrile results in an improved trans:cis ratio as compared to the initial ratio formed in the making of the base. Here the beginning product (the Tramadol base C produced in Example 1) had a trans:cis ratio of 89:11 whereas after converting to the hydrochloride followed by 3 rounds of crystallization from acetonitrile the ratio had been improved to 99.99:0.01.
