Gabapentin → Gabapentin Enacarbil

HRID 389359Notes

Reaction equation

HRID 389359 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. 1H NMR (CDCl3, 400 MHz): 1.15 (d, 6H), 1.40-1.55 (m, 10H), 1.45 (d, 3H), 2.32 (s, 2H), 2.49-2.56 (m, 1H), 3.23 (d, 2H), 5.41 (t, 1H), 6.75 (q, 1H). MS (ESI) m/z 330.29 (M+H+).

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-b221af7547ef43649a47d06e670366fa
Source dataset
uspto-grants-2013_02
Patent number
US08378137B2

Reaction notes

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