Citric Acid → 1403960-81-5

HRID 1424749Notes

Reaction equation

HRID 1424749 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[CH:8][CH:9]=[C:10]2[CH2:13][CH2:14][NH:15][C:16](=[O:18])[CH3:17])=[CH:5][CH:4]=1.[C:19]([OH:31])(=[O:30])[CH2:20][C:21]([CH2:26][C:27]([OH:29])=[O:28])([C:23]([OH:25])=[O:24])[OH:22]>CC(C)=O>[C:19]([OH:31])(=[O:30])[CH2:20][C:21]([CH2:26][C:27]([OH:29])=[O:28])([C:23]([OH:25])=[O:24])[OH:22].[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH:7]=[CH:8][CH:9]=[C:10]2[CH2:13][CH2:14][NH:15][C:16](=[O:18])[CH3:17])=[CH:5][CH:4]=1

Participants

4

Reactant 2

HCID 311Citric AcidHCID 82148Agomelatine

Product 1

HCID 665744421403960-81-5

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Conditions

Temperature
3.5 °C

Procedure

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.

Workup

  1. customto give a clear yellow solution
  2. additionwas added
  3. customto give a clear yellow solution
  4. concentrationThe solution was concentrated to approximately half its original volume
  5. customAn approximately 2 ml fraction was removed
  6. customplaced in an ultrasonic bath
  7. customcrystallisation
  8. customcrystallisation
  9. customto give a white suspension
  10. customthe white solid was isolated by filtration
  11. washwashed with cold diethyl ether
  12. customthen dried at 40° C. at a pressure of 150 mbar for 20 hours
  13. customThe isolated white solid (small bladed crystals) gave an XRPD pattern consistent with
  14. customof melting of approximately 123.5° C.

Sources & evidence

ORD record
ord-7352f4f70ddc4649a0f0b54a7bec8a23
Source dataset
uspto-grants-2015_01
Patent number
US08927771B2

Reaction notes

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