Hydrochloric Acid → HCID 69952816, compound

HRID 565701Notes

Reaction equation

HRID 565701 reaction equation
[NH2:1][C:2]1[C:3]([CH3:38])=[C:4]([CH3:37])[C:5]2[O:9][C:8]([CH2:11][N:12]3[CH2:17][CH2:16][CH:15]([C:18]([NH:20][CH2:21][CH:22]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=O)[CH2:14][CH2:13]3)([CH3:10])[CH2:7][C:6]=2[C:35]=1[CH3:36].[ClH:39].C(=O)([O-])O.[Na+]>O1CCCC1.O.C(OC(C)C)(C)C>[ClH:39].[ClH:39].[ClH:39].[NH2:1][C:2]1[C:3]([CH3:38])=[C:4]([CH3:37])[C:5]2[O:9][C:8]([CH2:11][N:12]3[CH2:17][CH2:16][CH:15]([CH2:18][NH:20][CH2:21][CH:22]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH2:14][CH2:13]3)([CH3:10])[CH2:7][C:6]=2[C:35]=1[CH3:36]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 22111029HCID 22111029, compound

Product 1

HCID 69952816HCID 69952816, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 21610435HCID 21610435, compoundSolvent

Procedure

To a solution of 1-[(5-amino-2,3-dihydro-2,4,6,7-tetramethylbenzofuran-2-yl)methyl]-N-(2,2-diphenylethyl)-4-piperidinecarboxamide (1.0 g) in tetrahydrofuran (20 mL) was added 12 mL of 1 M borane tetrahydrofuran complex solution in tetrahydrofuran dropwise with ice-cooling and the mixture was refluxed under nitrogen gas for 6 hours. After this reaction mixture was cooled with ice, 8 mL of 5N-hydrochloric acid was added dropwise, followed by stirring. The mixture was added dropwise to a suspension of sodium hydrogen carbonate (4 g) in water/diisopropyl ether for neutralization and extracted with 2 portions of ethyl acetate. The pooled organic layer was washed with saturated aqueous NaCl, dried over MgSO4, filtered, and concentrated. After the residue was dissolved in methanol, 10 mL of 5N-hydrochloric acid was added and the mixture was refluxed for 1 hour. After ice-cooling, the mixture was diluted with 20 mL of 5N-aqueous sodium hydroxide and extracted with 3 portions of diethyl ether. The pooled organic layer was washed with water and saturated aqueous NaCl, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (hexane/ethyl acetate/triethylamine=30:10:1 to 20:10:1) to recover 1-[(5-amino-2,3-dihydro-2,4,6,7-tetramethylbenzofuran-2-yl)methyl]-N-(2,2-diphenylethyl)-4-piperidinemethylamine. After this product was dissolved in methanol, a stoichiometric excess of 10% HCl solution in methanol was added dropwise and the resulting mixture was concentrated under reduced pressure to provide 0.74 g of the title compound.

Workup

  1. temperaturecooling
  2. temperaturethe mixture was refluxed under nitrogen gas for 6 hours
  3. additionwas added dropwise
  4. extractionextracted with 2 portions of ethyl acetate
  5. washThe pooled organic layer was washed with saturated aqueous NaCl
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. dissolutionAfter the residue was dissolved in methanol
  10. addition10 mL of 5N-hydrochloric acid was added
  11. temperaturethe mixture was refluxed for 1 hour
  12. temperatureAfter ice-cooling
  13. additionthe mixture was diluted with 20 mL of 5N-aqueous sodium hydroxide
  14. extractionextracted with 3 portions of diethyl ether
  15. washThe pooled organic layer was washed with water and saturated aqueous NaCl
  16. dry with materialdried over MgSO4
  17. filtrationfiltered
  18. concentrationconcentrated under reduced pressure
  19. customto recover 1-[(5-amino-2,3-dihydro-2,4,6,7-tetramethylbenzofuran-2-yl)methyl]-N-(2,2-diphenylethyl)-4-piperidinemethylamine
  20. dissolutionAfter this product was dissolved in methanol
  21. additiona stoichiometric excess of 10% HCl solution in methanol was added dropwise
  22. concentrationthe resulting mixture was concentrated under reduced pressure

Sources & evidence

ORD record
ord-cd51ee8ea5034d91a300d5806a8d72e2
Source dataset
uspto-grants-2001_01
Patent number
US06172085B2

Reaction notes

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