Sodium Carbonate → 4-(2-Methoxyphenyl)piperidine--hydrogen chloride (1/1)

HRID 1419567Notes

Reaction equation

HRID 1419567 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.[CH3:22][O:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1B(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][O:23][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 433294Lithium ChlorideHCID 27339582-Methoxyphenylboronic acidHCID 10991161Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylate

Product 1

HCID 171748754-(2-Methoxyphenyl)piperidine--hydrogen chloride (1/1)Yield 61.1%

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 (810 mg), 2-methoxyphenylboronic acid (519 mg), lithium chloride (405 mg) and aqueous sodium carbonate (2N, 3.5 mL) in 1,2-dimethoxyethane (20 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 and the solvent was evaporated under reduced pressure. The residue was purified by MPLC on silica gel, eluting with EtOAc/Hexane (5:95) and the residue was deprotected with ethanolic hydrogen chloride to give the title compound as a colorless solid (340 mg), δH (d6 -DMSO), 1.54-1.59 (2H, m), 1.77-1.81 (2H, m), 2.77 (2H, td, J 11.0, 1.0 Hz), 3.07 (1H, td, J 11.0, 1.0 Hz), 3.11 (2H, br m), 3.82 (3H, s), 6.85 (1H, d, J 6.0 Hz), 6.93 (1H, t, J 6.0 Hz), 7.15-7.21 (2H, m).

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)

Sources & evidence

ORD record
ord-4bc8cb570bdc439383c48b9813fc5ef2
Source dataset
uspto-grants-1999_03
Patent number
US05885999

Reaction notes

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