Hydrochloric Acid → Atomoxetine hydrochloride

HRID 2116842Notes

Reaction equation

HRID 2116842 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][C:7]=1[O:8][C@@H:9]([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[CH2:10][CH2:11][NH:12][CH3:13].C([O-])(=O)[C@H](C1C=CC=CC=1)O.[OH-].[Na+].[ClH:33].CC1C=CC=CC=1O[C@@H](C1C=CC=CC=1)CCNC>O.C(OCCCC)(=O)C>[CH3:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][C:7]=1[O:8][C@@H:9]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:10][CH2:11][NH:12][CH3:13].[ClH:33]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 54841AtomoxetineHCID 131727128HCID 131727128, compound

Product 1

HCID 54840Atomoxetine hydrochloride

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31272Butyl AcetateSolvent

Procedure

One mole of atomoxetine (S)-(+)-mandelate (88.6% w/w by potentiometric assay) was mixed under stirring with 2037.5 ml of n-butyl acetate and 2037.5 ml of water. Keeping the temperature between 20-25° C., 1.529 moles of 30% aqueous sodium hydroxide was added, and then the phases were separated. The organic phase was washed twice with 400 ml of water, then filtered on paper and used for the next step. While stirring and maintaining the temperature between about 22° C. and about 25° C. by means of water bath cooling, 1.1435 moles of aqueous hydrogen chloride (36%) was dropped on the atomoxetine base solution obtained above. The hydrochloride then crystallized. The obtained suspension was stirred at about 25° C. for one hour; the solid was collected by filtration, and washed twice with 345 ml of n-butyl acetate. The solid collected was dried for 18 hours at 70° C. under vacuum. Enantiomeric purities are summarized in the following table:

Workup

  1. custombetween 20-25° C.
  2. customthe phases were separated
  3. washThe organic phase was washed twice with 400 ml of water
  4. filtrationfiltered on paper
  5. temperaturemaintaining the temperature between about 22° C. and about 25° C. by means of water bath
  6. temperaturecooling
  7. customobtained above
  8. customThe hydrochloride then crystallized
  9. stirringThe obtained suspension was stirred at about 25° C. for one hour
  10. filtrationthe solid was collected by filtration
  11. washwashed twice with 345 ml of n-butyl acetate
  12. customThe solid collected
  13. customwas dried for 18 hours at 70° C. under vacuum

Sources & evidence

ORD record
ord-a983424e5880433e80738a88fa06ca5c
Source dataset
uspto-grants-2008_10
Patent number
US07439398B2

Reaction notes

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