Ammonium formate → Gabapentin Enacarbil

HRID 1767289

Reaction equation

HRID 1767289 reaction equation
C([O-])=O.[NH4+].[C:5]([O:10][CH:11]([O:13][C:14]([NH:16][CH2:17][C:18]1([CH2:24][C:25]([O:27]CC=C)=[O:26])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1)=[O:15])[CH3:12])(=[O:9])[CH:6]([CH3:8])[CH3:7]>C(O)C.[Pd]>[C:5]([O:10][CH:11]([O:13][C:14]([NH:16][CH2:17][C:18]1([CH2:24][C:25]([OH:27])=[O:26])[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1)=[O:15])[CH3:12])(=[O:9])[CH:6]([CH3:8])[CH3:7]

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 9999163Allyl 1-{[(alpha-Isobutanoyloxyethoxy)carbonyl]aminomethyl}-1-Cyclohexane Acetate

Product 1

HCID 9883933Gabapentin Enacarbil

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a stirred suspension of ammonium formate (3.4 g, 54 mmol) in ethanol (34 mL), was added compound (15) (10 g, 27 mmol) together with 10% Pd/C (1 g) under a nitrogen atmosphere. After one hour, the reaction mixture was filtered and the catalyst washed with ethanol (2×10 mL). The filtrates were combined and evaporated. The crude product was dissolved in diethyl ether (150 mL) and the organic phase was washed with 2N HCl (100 mL), water (100 mL) and brine (100 mL). The ether layer was dried over anhydrous sodium sulfate and concentrated to give a viscous liquid that crystallized upon standing. The product was recrystallized using 1:10 ethyl acetate:heptane (100 mL) to give the product (11) as a white, crystalline solid (7.9 g, 88%), m.p 63–64° C.

Workup

  1. filtrationthe reaction mixture was filtered
  2. washthe catalyst washed with ethanol (2×10 mL)
  3. customevaporated
  4. dissolutionThe crude product was dissolved in diethyl ether (150 mL)
  5. washthe organic phase was washed with 2N HCl (100 mL), water (100 mL) and brine (100 mL)
  6. dry with materialThe ether layer was dried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customto give a viscous liquid that
  9. customcrystallized
  10. customThe product was recrystallized

Sources & evidence

ORD record
ord-2f6a36ef9d804b6f8ca88b24d51148a4
Source dataset
uspto-grants-2007_06
Patent number
US07232924B2

Linked notes

Loading…