Ammonia → Gabapentin

HRID 1005383Notes

Reaction equation

HRID 1005383 reaction equation
N.Cl.[NH2:3][CH2:4][C:5]1([CH2:11][C:12]([OH:14])=[O:13])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1>O>[NH2:3][CH2:4][C:5]1([CH2:11][C:12]([OH:14])=[O:13])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1

Participants

4

Reactant 2

HCID 222AmmoniaHCID 6453919Gabapentin hydrochloride

Product 1

HCID 3446GabapentinYield 71%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
-10 °C

Procedure

A 3 m long and 200 mm wide chromatography column is filled with 50 L of ion exchanger resin (IRA 68). The resin is regenerated with a solution of 14 L of concentrated aqueous ammonia in 300 L of demineralized water and subsequently washed with 150 L of demineralized water. As soon as the eluate has reached a pH of 6.8 and chloride can no longer be detected, a solution of 8.67 kg (40.8 mole) 1-aminomethyl-1-cyclohexaneacetic acid hydrochloride in 43 L of demineralized water is applied to the column. The free amino acid is eluted with demineralized water at a rate of 1.5 L/min and collected in 15 fractions each of 15 L. The combined fractions are evaporated at 6.65 KPa and at most 45° C. The white solid residue is introduced into 20 L of methanol, heated to reflux, filtered, and cooled to -10° C. The product which crystallizes out is centrifuged, washed with 10 L of cold methanol, and dried for 17 hours at 30° to 40° C. 4.9 kg (71% of theory) of pure 1-(aminomethyl)-cyclohexaneacetic acid are obtained; m.p. 165° C. A further 0.8 kg can be obtained by working up the mother liquors.

Workup

  1. washsubsequently washed with 150 L of demineralized water
  2. washThe free amino acid is eluted with demineralized water at a rate of 1.5 L/min
  3. customcollected in 15 fractions each of 15 L
  4. customThe combined fractions are evaporated at 6.65 KPa and at most 45° C
  5. additionThe white solid residue is introduced into 20 L of methanol
  6. temperatureheated
  7. temperatureto reflux
  8. filtrationfiltered
  9. customThe product which crystallizes out
  10. washwashed with 10 L of cold methanol
  11. customdried for 17 hours at 30° to 40° C

Sources & evidence

ORD record
ord-e3334e98ac5e4b8b9e364e6711ca7478
Source dataset
uspto-grants-2000_04
Patent number
US06054482

Reaction notes

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