Water → 1-{2-{N-{3-[2-(4-Fluorophenyl)-1,3-dioxolan-2-yl]-propyl}-N-methylamino}ethyl}-4-(3-chlorophenoxy)piperidine dihydrochloride

HRID 463309Notes

Reaction equation

HRID 463309 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].C(O)(=O)C(O)=O.[F:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2([CH2:25][CH2:26][CH2:27][N:28]([CH2:30][C:31]([N:33]3[CH2:38][CH2:37][CH:36]([O:39][C:40]4[CH:45]=[CH:44][CH:43]=[C:42]([Cl:46])[CH:41]=4)[CH2:35][CH2:34]3)=O)[CH3:29])[O:24][CH2:23][CH2:22][O:21]2)=[CH:16][CH:15]=1.O.[OH-].[Na+]>C1COCC1>[ClH:46].[ClH:46].[F:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2([CH2:25][CH2:26][CH2:27][N:28]([CH2:30][CH2:31][N:33]3[CH2:38][CH2:37][CH:36]([O:39][C:40]4[CH:45]=[CH:44][CH:43]=[C:42]([Cl:46])[CH:41]=4)[CH2:35][CH2:34]3)[CH3:29])[O:21][CH2:22][CH2:23][O:24]2)=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 202831291-{N-{3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl}-N-methylaminoacetyl}-4-(3-chlorophenoxy)piperidine oxalateHCID 21226445Aluminium lithium hydride

Product 1

HCID 202830781-{2-{N-{3-[2-(4-Fluorophenyl)-1,3-dioxolan-2-yl]-propyl}-N-methylamino}ethyl}-4-(3-chlorophenoxy)piperidine dihydrochloride

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension prepared from 3.00 g (39.5 mmol) of 50% lithium aluminum hydride in oil and 100 ml of dry THF and maintained at 0° was added dropwise a solution of 1-{N-{3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl}-N-methylaminoacetyl}-4-(3-chlorophenoxy)piperidine oxalate in 100 ml of dry THF. The mixture was heated at reflux under nitrogen for 12 hours, allowed to cool to room temperature and subsequently cooled in an ice bath. To the mixture was added slowly, dropwise 3 ml of water followed by 3 ml of 15% sodium hydroxide and 9 ml of water. The suspension was filtered and washed with 150 ml of THF, and the THF was evaporated. The residue was extracted with ether, washed with saturated sodium chloride and dried over potassium carbonate. The yield of the dihydrochloride was 9.36 g (79%). Crystallization from ethanol provided analytically pure material.

Workup

  1. temperaturemaintained at 0°
  2. temperatureThe mixture was heated
  3. temperatureat reflux under nitrogen for 12 hours
  4. temperaturesubsequently cooled in an ice bath
  5. additionTo the mixture was added slowly
  6. filtrationThe suspension was filtered
  7. washwashed with 150 ml of THF
  8. customthe THF was evaporated
  9. extractionThe residue was extracted with ether
  10. washwashed with saturated sodium chloride
  11. dry with materialdried over potassium carbonate
  12. customCrystallization from ethanol
  13. customprovided analytically pure material

Sources & evidence

ORD record
ord-361e5f99906a455797087e9713d04901
Source dataset
uspto-grants-1985_05
Patent number
US04518713

Reaction notes

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