Sodium Carbonate → Erythromycin ethyl succinate

HRID 1508609

Reaction equation

HRID 1508609 reaction equation
[CH3:1][CH2:2][C@H:3]1[O:18][C:16](=[O:17])[C@H:15]([CH3:19])[C@@H:14]([O:20][C@@H:21]2[O:26][C@@H:25]([CH3:27])[C@H:24]([OH:28])[C@@:23]([O:30][CH3:31])([CH3:29])[CH2:22]2)[C@H:13]([CH3:32])[C@@H:12]([O:33][C@@H:34]2[O:39][C@H:38]([CH3:40])[CH2:37][C@H:36]([N:41]([CH3:43])[CH3:42])[C@H:35]2[OH:44])[C@@:11]([OH:46])([CH3:45])[CH2:10][C@@H:9]([CH3:47])[C:7](=[O:8])[C@H:6]([CH3:48])[C@@H:5]([OH:49])[C@@:4]1([OH:51])[CH3:50].C(S)#N.CC[C@H]1OC(=O)[C@H](C)[C@@H:68]([O:74][C@@H:75]2[O:80][C@@H](C)[C@H:78]([OH:82])[C@@:77](OC)(C)[CH2:76]2)[C@H:67](C)[C@@H](O[C@@H]2O[C@H](C)C[C@H](N(C)C)[C@H]2O)[C@@](O)(C)C[C@@H](C)C(=O)[C@H](C)[C@@H](O)[C@@]1(O)C.C(=O)(O)[O-].[Na+].C(=O)([O-])[O-].[Na+].[Na+].C(=O)([O-])[O-].[K+].[K+]>CCOCC.O>[CH3:1][CH2:2][C@H:3]1[O:18][C:16](=[O:17])[C@H:15]([CH3:19])[C@@H:14]([O:20][C@@H:21]2[O:26][C@@H:25]([CH3:27])[C@H:24]([OH:28])[C@@:23]([O:30][CH3:31])([CH3:29])[CH2:22]2)[C@H:13]([CH3:32])[C@@H:12]([O:33][C@@H:34]2[O:39][C@H:38]([CH3:40])[CH2:37][C@H:36]([N:41]([CH3:42])[CH3:43])[C@H:35]2[O:44][C:78]([CH2:77][CH2:76][C:75]([O:74][CH2:68][CH3:67])=[O:80])=[O:82])[C@@:11]([OH:46])([CH3:45])[CH2:10][C@@H:9]([CH3:47])[C:7](=[O:8])[C@H:6]([CH3:48])[C@@H:5]([OH:49])[C@@:4]1([OH:51])[CH3:50]

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 11430Potassium CarbonateHCID 12560ErythromycinHCID 83938Erythromycin ThiocyanateHCID 516892Sodium Bicarbonate

Product 1

HCID 443953Erythromycin ethyl succinate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

or method B: in a reaction vessel, one or more of a C1-C6 lower alcohol, a C2-C6 lower nitrile, a C3-C8 lower ketone or C2-C8 lower ether is used as a solvent, to the solvent is added one or more of erythromycin thiocyanate or erythromycin thiocyanate hydrate, erythromycin lactate, stirred, added sodium bicarbonate or sodium carbonate or potassium carbonate, and water, allowed to react with stirring for 1-3 hours, added dropwise an aqueous solution of an acid or a base, stirred to control the pH value at about 7.0-8.5; the organic phase is precipitated and separated; to the organic phase is added sodium bicarbonate or sodium carbonate or potassium carbonate, and water, stirred, cooled to 20° C. or below, added monoethyl succinate halide, including monoethyl succinate chloride or monoethyl succinate bromide, allowed to react, monitored by TLC until the reaction is complete; to the resultant is added an acid or a base to control the pH value at about 7.0-8.5; the organic phase is precipitated and separated; to the organic phase is added water, cooled to −20° C.-10° C., upon the solid is precipitated completely, the mixture is filtered, the resulting solid is recrystalized with water and one or more of a C1-C6 lower alcohol, a C2-C6 lower nitrile, a C2-C8 lower ether, a C3-C8 lower ketone or C1-C6 lower halogenated hydrocarbons as solvent once or more times, cooled to −20° C.-10° C., filtered, dried to obtain erythromycin ethylsuccinate crystalline hydrate.

Workup

  1. additionis added one
  2. customto react
  3. additionadded dropwise an aqueous solution of an acid
  4. stirringa base, stirred
  5. customthe organic phase is precipitated
  6. customseparated
  7. additionto the organic phase is added sodium bicarbonate or sodium carbonate or potassium carbonate, and water
  8. stirringstirred
  9. temperaturecooled to 20° C. or below
  10. additionadded monoethyl succinate halide
  11. customto react
  12. additionto the resultant is added an acid
  13. customthe organic phase is precipitated
  14. customseparated
  15. additionto the organic phase is added water
  16. temperaturecooled to −20° C.-10° C., upon the solid
  17. customis precipitated completely
  18. filtrationthe mixture is filtered
  19. customthe resulting solid is recrystalized with water and one or more of a C1-C6 lower alcohol
  20. temperaturea C2-C6 lower nitrile, a C2-C8 lower ether, a C3-C8 lower ketone or C1-C6 lower halogenated hydrocarbons as solvent once or more times, cooled to −20° C.-10° C.
  21. filtrationfiltered
  22. customdried

Sources & evidence

ORD record
ord-e3150fef325d4fa8aa271398501c6ae5
Source dataset
uspto-grants-2015_12
Patent number
US09221862B2

Linked notes

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