Hydrochloric Acid → HCID 178508914, compound

HRID 472019Notes

Reaction equation

HRID 472019 reaction equation
[CH2:1]1[NH:6][C:5]2[NH:7][C:8]([NH2:12])=[N:9][C:10](=[O:11])[C:4]=2[N:3]([CH:13]=[O:14])[C@H:2]1[CH2:15][NH:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]([NH:25][C@H:26]([C:32]([O-:34])=[O:33])[CH2:27][CH2:28][C:29]([O-:31])=[O:30])=[O:24])=[CH:19][CH:18]=1.O.O.O.O.O.[Ca+2].C(=O)([O-])[O-].[Na+].[Na+].C(=O)([O-])[O-].[Ca+2].Cl>O.C(O)(C)C.C(O)(=O)C>[CH2:1]1[NH:6][C:5]2[NH:7][C:8]([NH2:12])=[N:9][C:10](=[O:11])[C:4]=2[N:3]([CH:13]=[O:14])[C@H:2]1[CH2:15][NH:16][C:17]1[CH:18]=[CH:19][C:20]([C:23]([NH:25][C@H:26]([C:32]([OH:34])=[O:33])[CH2:27][CH2:28][C:29]([OH:31])=[O:30])=[O:24])=[CH:21][CH:22]=1

Participants

8

Reactant 4

HCID 313Hydrochloric Acid3×HCID 10112Calcium CarbonateHCID 10340Sodium CarbonateHCID 178508915HCID 178508915, compound

Product 1

HCID 178508914HCID 178508914, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×HCID 3776IsopropanolSolvent

Conditions

Temperature
40 °C

Procedure

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.

Workup

  1. temperatureto maintain the pH of the system at a value of about 8.0
  2. filtrationthe obtained sodium levofolinate solution is clarified by fine filtration
  3. additionThe filtered solution is diluted with water to a volume of 850 L and 51 L of isopropanol
  4. additionare added
  5. customthus forming a first solution
  6. additionThe first solution is then progressively added, during 1 hour
  7. temperaturepreviously heated at 45° C
  8. additionDuring this addition
  9. additionkept in the range between 3.5 and 4.0 by progressive addition of 50 L of a 25% b.w
  10. customslowly decreased to 35° C
  11. additionAt the end of the addition phase (i.e., the operation of adding the first solution to the hydroalcoholic batch), the obtained solution
  12. customis kept at 35° C.
  13. stirringunder stirring
  14. customLevofolinic acid crystallizes out of the obtained solution during the addition phase
  15. stirringthe subsequent stirring period

Sources & evidence

ORD record
ord-a68a12b5b22a42438ebdd443f4a7dda9
Source dataset
uspto-grants-2014_01
Patent number
US08633202B2

Reaction notes

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