Hydrochloric Acid → HCID 178508914, compound

Participants

Reaction Conditions

Reaction Steps

100 kg of calcium levofolinate pentahydrate (166 mol) are suspended in 500 litres (L) of purified water. The suspension is heated at 40° C. and is then decalcificated by addition of 25 kg of sodium carbonate (236 mol); acetic acid is added to maintain the pH of the system at a value of about 8.0. The formed calcium carbonate is eliminated by centrifugation and the obtained sodium levofolinate solution is clarified by fine filtration. The filtered solution is diluted with water to a volume of 850 L and 51 L of isopropanol are added thereto, thus forming a first solution. The first solution is then progressively added, during 1 hour under stirring, to a hydroalcoholic batch formed by 350 L of water and 35 L of isopropanol previously heated at 45° C. During this addition, the pH is monitored and kept in the range between 3.5 and 4.0 by progressive addition of 50 L of a 25% b.w. solution of HCl; the temperature is in its turn slowly decreased to 35° C. At the end of the addition phase (i.e., the operation of adding the first solution to the hydroalcoholic batch), the obtained solution is kept at 35° C. under stirring, while controlling the pH with further additions of the same HCl solution used before, until a stable value of 4.0 is reached; a total of 50 liters of HCl solution is added in the two phases. Levofolinic acid crystallizes out of the obtained solution during the addition phase and the subsequent stirring period. The crystallized levofolinic acid is then isolated by centrifugation, washed with water and dried under reduced pressure. 80 kg of product are obtained.

Provenance & Evidence