Sodium Carbonate → 4-(2-Methylphenyl)piperidine hydrochloride

HRID 1419585Notes

Reaction equation

HRID 1419585 reaction equation
C(OC([N:8]1[CH2:13][CH:12]=[C:11](OS(C(F)(F)F)(=O)=O)[CH2:10][CH2:9]1)=O)(C)(C)C.[CH:22]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1B(O)O)=O.[Cl-:33].[Li+].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[ClH:33].[CH3:22][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[CH:11]1[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 2921892-Formylphenylboronic acidHCID 433294Lithium ChlorideHCID 10991161Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylate

Product 1

HCID 219369564-(2-Methylphenyl)piperidine hydrochlorideYield 72.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

Tetrakis(triphenylphosphine)palladium (0) (100 mg) was added to a degassed mixture of 1-t-butoxycarbonyl-4-trifluoromethanesulfonyloxy-1,2,3,6-tetrahydropyridine (1.32 g), 2-formylphenylboronic acid (850 mg), lithium chloride (504 mg) and aqueous sodium carbonate (2N, 5.47 mL) in 1,2-dimethoxyethane (30 mL). The resulting solution was heated under reflux for 3 h., cooled to room temperature and the solvent was evaporated under reduced pressure. The residue was partitioned between ethyl acetate and aqueous sodium carbonate (2M) and the organic layer was separated, dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was dissolved in ethanol, palladium on carbon (10%) was added and the mixture was shaken under hydrogen (50 psi.) for 3 h. The mixture was filtered through Hyflo, the solvent was evaporated under reduced pressure and the residue was purified by MPLC on silica gel, eluting with EtOAc/Hexane (5:95). The residue was dissolved in ethanolic hydrogen chloride (50 mL) and stirred at room temperature for 30 min. The solvent was evaporated under reduced pressure to give the title compound as a colorless solid (610 mg). m/e (ES+) 176 (MH+).

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureunder reflux for 3 h.
  3. customthe solvent was evaporated under reduced pressure
  4. customThe residue was partitioned between ethyl acetate and aqueous sodium carbonate (2M)
  5. customthe organic layer was separated
  6. dry with materialdried (MgSO4)
  7. customthe solvent was evaporated under reduced pressure
  8. dissolutionThe residue was dissolved in ethanol
  9. additionpalladium on carbon (10%) was added
  10. filtrationThe mixture was filtered through Hyflo
  11. customthe solvent was evaporated under reduced pressure
  12. customthe residue was purified by MPLC on silica gel
  13. washeluting with EtOAc/Hexane (5:95)
  14. dissolutionThe residue was dissolved in ethanolic hydrogen chloride (50 mL)
  15. stirringstirred at room temperature for 30 min
  16. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-00aa6e2069c1454291f73fea67ee818c
Source dataset
uspto-grants-1999_03
Patent number
US05885999

Reaction notes

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