(1-Aminomethyl)-cyclohexaneacetic acid hydrochloride hydrate → Gabapentin monohydrate

HRID 1087986Notes

Reaction equation

HRID 1087986 reaction equation
O.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>[OH2:13].[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

3

Reactant 1

HCID 22664988(1-Aminomethyl)-cyclohexaneacetic acid hydrochloride hydrate

Product 1

HCID 14598836Gabapentin monohydrateYield 1,580.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
19 °C

Procedure

A solution of 122 Kg (57.5 moles) of 1-(aminomethyl)-cyclohexaneacetic acid monohydrochloride hydrate (4:4:1) in 472 Kg of deionized water is filtered to remove any insoluble material or extracted with an organic solvent such as dichloromethane and then is applied to the top of the ion exchange column and eluted with 3750 Kg of deionized water. The presence of chloride ion is tested for using silver nitrate solution and the product is tested for by using thin layer chromatography. The eluate is concentrated in a 500 gallon glass-lined still at about 29-31 inches of vacuum and wall temperature of <50° C. A total of 3500 Kg of water is removed. The resulting slurry is cooled to about 18-20° C. and 248.5 Kg of 2-propanol is added. The slurry is cooled at -12--8° C. for 16 hours, centrifuged and washed with 2-propanol. The precipitate is dried in vacuo about 29-31 inches at 25-30° C. to yield 86 Kg of 1-(aminomethyl)-cyclohexaneacetic acid hydrate (1:1).

Workup

  1. customto remove any insoluble material
  2. extractionextracted with an organic solvent such as dichloromethane
  3. washeluted with 3750 Kg of deionized water
  4. concentrationThe eluate is concentrated in a 500 gallon glass-lined still at about 29-31 inches of vacuum and wall temperature of <50° C
  5. customA total of 3500 Kg of water is removed
  6. addition248.5 Kg of 2-propanol is added
  7. temperatureThe slurry is cooled at -12--8° C. for 16 hours
  8. washwashed with 2-propanol
  9. customThe precipitate is dried in vacuo about 29-31 inches at 25-30° C.

Sources & evidence

ORD record
ord-1ccf7b702078438d888f67f92484f344
Source dataset
uspto-grants-1990_10
Patent number
US04960931

Reaction notes

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