(1-Cyanocyclohexyl)acetic acid → Gabapentin

HRID 2379511Notes

Reaction equation

HRID 2379511 reaction equation
[C:1]([C:3]1([CH2:9][C:10]([OH:12])=[O:11])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1)#[N:2].[H][H]>CO.[Rh].[Pd]>[NH2:2][CH2:1][C:3]1([CH2:9][C:10]([OH:12])=[O:11])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1

Participants

6

Reactant 2

HCID 11073797(1-Cyanocyclohexyl)acetic acidHCID 178418361HCID 178418361, compound

Product 1

HCID 3446GabapentinYield 79.7%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 23948RhodiumCatalystHCID 887MethanolSolvent2×

Procedure

One gram of 10% rhodium on carbon, containing 1% palladium, (Pearlman, W. M., Tetrahedron Letters, pages 1663-1664 (1967)) is slurried in 30 ml methanol and reduced under hydrogen in a Parr shaker. 1-Cyanocyclohexaneacetic acid (16.7 g, 0.1 mol) is dissolved in 40 ml methanol and combined with the reduced catalyst. The mixture is placed under 50 pounds per square inch gauge (psig) hydrogen and shaken for two hours at room temperature. The catalyst is removed by filtration, and the filtrate is condensed to a volume of 25 ml by vacuum distillation. Isopropanol, 100 ml, is added and an additional 25 to 50 ml of solvent is removed by vacuum distillation. The resultant slurry is cooled at 0° to 5° C. for 24 hours and filtered and dried to give 13.65 g (79% of theory) of 1-(aminomethyl)-cyclohexaneacetic acid; mp 162°-163° C.

Workup

  1. customThe catalyst is removed by filtration
  2. customcondensed to a volume of 25 ml
  3. distillationby vacuum distillation
  4. additionIsopropanol, 100 ml, is added
  5. customan additional 25 to 50 ml of solvent is removed by vacuum distillation
  6. temperatureThe resultant slurry is cooled at 0° to 5° C. for 24 hours
  7. filtrationfiltered
  8. customdried

Sources & evidence

ORD record
ord-a18038c89b334073881fda0ceb439588
Source dataset
uspto-grants-1994_11
Patent number
US05362883

Reaction notes

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