Gabapentin → Gabapentin Enacarbil

HRID 1675984Notes

Reaction equation

HRID 1675984 reaction equation
[CH2:1]1[CH2:6][CH2:5][C:4]([CH2:11][NH2:12])([CH2:7][C:8]([OH:10])=[O:9])[CH2:3][CH2:2]1.C(=O)(O)[O-].[Na+].[C:18]([O:23][CH:24]([O:26][C:27](OC1CC(=O)NC1=O)=[O:28])[CH3:25])(=[O:22])[CH:19]([CH3:21])[CH3:20]>O.C(#N)C.C(OCC)C>[C:18]([O:23][CH:24]([O:26][C:27]([NH:12][CH2:11][C:4]1([CH2:7][C:8]([OH:10])=[O:9])[CH2:3][CH2:2][CH2:1][CH2:6][CH2:5]1)=[O:28])[CH3:25])(=[O:22])[CH:19]([CH3:21])[CH3:20]

Participants

7

Reactant 3

HCID 3446GabapentinHCID 516892Sodium BicarbonateHCID 66743414[(1-Isobutanoyloxyethoxy)carbonyloxy]succinimide

Product 1

HCID 9883933Gabapentin EnacarbilYield 96%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of gabapentin (1.7 g, 10 mmol) and sodium bicarbonate (20 mmol) in water (40 mL) was added a solution of compound (10) (2.73 g, 10 mmol) in acetonitrile (20 mL) over 1 min. The reaction was stirred at ambient temperature for 16 h. The reaction mixture was diluted with diethyl ether (100 mL) and washed with 0.1 M aqueous potassium bisulfate (3×100 mL). The organic phase was separated, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to afford the title compound (12) as a white solid (2.7 g, 96%). The product was recrystallized by dissolution in 1:10 ethyl acetate:heptane (10 mL) at 60° C., followed by slow cooling to 4° C. The white crystalline product was isolated by filtration. Melting point: 63-64° C.

Workup

  1. washwashed with 0.1 M aqueous potassium bisulfate (3×100 mL)
  2. customThe organic phase was separated
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-051901597d044e4caf9cd3efaa4e7679
Source dataset
uspto-grants-2011_08
Patent number
US08003809B2

Reaction notes

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