Hydrochloric Acid → Eslicarbazepine

HRID 526677Notes

Reaction equation

HRID 526677 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+].Cl.[OH-].[Na+]>ClCCl>[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

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 34312OxcarbazepineHCID 4311764Sodium borohydride

Product 1

HCID 9881504EslicarbazepineYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of phenyl boronic acid (19.4 gm), D-(−)-tartaric acid (23.8 gm), calcium hydride (13.3 gm) in acetonitrile (300 mL) was heated to about 80-85° C. for about 1 hr. The reaction mass was cooled to 25-30° C. (‘Solution X’). A solution of oxcarbazepine (20 gm) in acetonitrile (100 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 (4.5 gm) was added at about 30-35° C. The reaction mass was stirred at the same temperature for about 8 hrs. The pH of the resulting solution was adjusted to 1-2 by adding HCl (3N, 200 mL) followed by stirring for about 30 minutes. To the resulting solution, NaOH (20% w/v) solution was added to adjust the pH at about 12-13. Dichloromethane was added to the resulting solution followed by stirring. The organic layer was separated and distilled to obtain the title compound (Yield: 91%; HPLC purity: 98.6%; Chiral purity: 92.5%).

Workup

  1. stirringThe reaction mass was stirred at the same temperature for about 8 hrs
  2. stirringby stirring for about 30 minutes
  3. stirringby stirring
  4. customThe organic layer was separated
  5. distillationdistilled

Sources & evidence

ORD record
ord-53a7f38c784b4d279557b2ec92375e28
Source dataset
uspto-grants-2016_05
Patent number
US09346760B2

Reaction notes

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