Oxcarbazepine → Eslicarbazepine

HRID 526676Notes

Reaction equation

HRID 526676 reaction equation
[CH:1]1[CH:2]=[CH:3][C:4]2[N:16]([C:17]([NH2:19])=[O:18])[C:15]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[C:8](=[O:9])[CH2:7][C:5]=2[CH:6]=1.[BH4-].[Na+]>>[CH:1]1[CH:2]=[CH:3][C:4]2[N:16]([C:17]([NH2:19])=[O:18])[C:15]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[C@@H:8]([OH:9])[CH2:7][C:5]=2[CH:6]=1

Participants

3

Reactant 2

HCID 34312OxcarbazepineHCID 4311764Sodium borohydride

Product 1

HCID 9881504EslicarbazepineYield 70%

Conditions

Temperature
57.5 °C

Procedure

A solution of phenyl boronic acid (48.5 gm), D-(−)-tartaric acid (59.4 gm), calcium hydride (33.2 gm) in acetonitrile (750 mL) was heated to about 80-85° C. for about 1 hr. The reaction mass was cooled to about 25-30° C. (‘Solution X’). A solution of oxcarbazepine (50 gm) in acetonitrile (250 mL) was prepared separately. ‘Solution X’ obtained above was added to the solution of oxcarbazepine followed by stirring the reaction mass for about 2 hrs. To the resulting solution sodium borohydride (59.4 gm) was added at about 30-35° C. The reaction mass was stirred at the same temperature for about 8-10 hrs followed by distillation of solvent. To the resulting residue water (1000 mL) was added. The pH of the resulting solution was adjusted to about 12-13 by adding NaOH solution. The reaction mass was heated to about 55-60° C. followed by stirring at the same temperature for about 1 hr. consequently, cooled the reaction mass to about 20-25° C. The reaction mass was stirred at the same temperature for about 4 hrs. The reaction mass was again cooled to about 10-15° C. and stirred for about 3 hrs. The resulting solid (35 gm) was filtered, washed and dried to obtain the title compound (Yield: 70%; HPLC purity: 99.5%; Chiral purity: 96.4%; d0.9 114.3 μm, d0.5 53.1 μm, d0.1 22 μm).

Workup

  1. stirringThe reaction mass was stirred at the same temperature for about 8-10 hrs
  2. distillationfollowed by distillation of solvent
  3. additionTo the resulting residue water (1000 mL) was added
  4. additionby adding NaOH solution
  5. stirringby stirring at the same temperature for about 1 hr
  6. temperatureconsequently, cooled the reaction mass to about 20-25° C
  7. stirringThe reaction mass was stirred at the same temperature for about 4 hrs
  8. temperatureThe reaction mass was again cooled to about 10-15° C.
  9. stirringstirred for about 3 hrs
  10. filtrationThe resulting solid (35 gm) was filtered
  11. washwashed
  12. customdried

Sources & evidence

ORD record
ord-7e4e51720b0b468a833a92cff2f14c46
Source dataset
uspto-grants-2016_05
Patent number
US09346760B2

Reaction notes

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