Citric Acid → 1403960-81-5

Participants

Reaction Conditions

Reaction Steps

100 g N-[2-(7-methoxy-1-naphthyl)ethyl]acetamide was dissolved in 240m1 acetone at 60° C. to give a clear yellow solution. A suspension of 78.9 g citric acid in 300 ml acetone at 40° C. was added to give a clear yellow solution. The solution was concentrated to approximately half its original volume and cooled to approximately 2-5° C. An approximately 2 ml fraction was removed and placed in an ultrasonic bath to induce crystallisation. The cloudy fraction was returned to the mother solution and over 1 hour crystallisation occurred to give a white suspension. The suspension was maturated by stirring at ambient temperature for 48 hours and the white solid was isolated by filtration and washed with cold diethyl ether then dried at 40° C. at a pressure of 150 mbar for 20 hours. The final yield of dry material was 148 g (83%) and the purity of agomelatin in the solid was 99.9% with no impurities above 0.1% by UPLC. The isolated white solid (small bladed crystals) gave an XRPD pattern consistent with that shown in FIG. 1 and a DSC thermograph consistent with that shown in FIG. 2 with an onset of melting of approximately 123.5° C.

Provenance & Evidence