p-Toluenesulfonic acid → HCID 53697556, compound

HRID 427344Notes

Reaction equation

HRID 427344 reaction equation
[CH2:1]([Li])[CH2:2][CH2:3]C.[CH3:6][N:7]1[CH2:12][CH2:11][C:10](=O)[CH2:9][CH2:8]1.[C:14]1([CH3:24])[CH:19]=[CH:18][C:17](S(O)(=O)=O)=[CH:16][CH:15]=1.[CH:25]([O-:27])=O.[NH4+:28]>O1CCCC1.C1(C)C=CC=CC=1.CO.O.[Pd]>[NH2:28][C@@H:16]1[CH2:17][CH2:18][C:19]2[C:14](=[C:24]([CH:10]3[CH2:11][CH2:12][N:7]([CH3:6])[CH2:8][CH2:9]3)[CH:1]=[CH:2][C:3]=2[O:27][CH3:25])[CH2:15]1

Participants

10

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 740491-Methyl-4-piperidoneHCID 2723923Ammonium formateHCID 178418339Butyllithium

Product 1

HCID 53697556HCID 53697556, compoundYield 95%

Reagents, catalysts & solvents 5

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

(R)-8-Bromo-2-N,N-dibenzylamino-5-methoxy-1,2,3,4-tetrahydronaphthalene (6.8 g, 16 mmol) was dissolved in anhydrous tetrahydrofuran (100 mL) under nitrogen atmosphere. The solution was cooled to −78° C. and n-butyllithium (11.7 mL, 1.6 M, 19 mmol) was added dropwise during 3 minutes. The mixture was stirred for 5 min and N-methyl-4-piperidone (5.4 g, 48 mmol) was added during 3 min. The cooling bath was removed and the temperature was allowed to rise to 0° C. before the reaction was quenched by the addition of water. The layers were separated and the organic layer was dried (MgSO4). The solvent was removed in vacuo to give a residue which was purified by crystallization (ethyl acetate/hexane). Yield 5.8 g (77%): EIMS (70 eV) m/z (relative intensity) 470 (2, M+). The crystals (4.6 g, 9.8 mmol) were dissolved in toluene and p-toluenesulfonic acid (2.8 g, 15 mmol) was added and the reaction was stirred at reflux for 8 h under nitrogen with azeotropic removal of water in a Dean-Stark trap. The cooled reaction mixture was washed with a 2 M aqueous solution of sodium hydroxide and the phases were separated, dried (MgSO4), filtered and evaporated in vacuo to give a viscous oil: EIMS (70 eV) m/z (relative intensity) 452 (1, M+). The oil (0.6 g, 1.3 mmol) was dissolved in a solution of methanol (30 mL) and water (15 mL) and ammonium formate (1.7 g, 26 mmol) and palladium (0.3 g: 10% on activated carbon) was added. The mixture was refluxed for 45 min and the palladium was filtered off. The solvent was evaporated in vacuo and the residue was partitioned between ethyl acetate and a 2 M solution of ammonium hydroxide. The organic phase was separated, dried (Na2SO4), filtered and evaporated in vacuo to give 300 mg (95% yield) of the title compound.

Workup

  1. customThe cooling bath was removed
  2. customto rise to 0° C. before the reaction
  3. customwas quenched by the addition of water
  4. customThe layers were separated
  5. dry with materialthe organic layer was dried (MgSO4)
  6. customThe solvent was removed in vacuo
  7. customto give a residue which
  8. customwas purified by crystallization (ethyl acetate/hexane)
  9. stirringthe reaction was stirred
  10. customThe cooled reaction mixture
  11. washwas washed with a 2 M aqueous solution of sodium hydroxide
  12. customthe phases were separated
  13. dry with materialdried (MgSO4)
  14. filtrationfiltered
  15. customevaporated in vacuo
  16. customto give a viscous oil
  17. additionwas added
  18. temperatureThe mixture was refluxed for 45 min
  19. filtrationthe palladium was filtered off
  20. customThe solvent was evaporated in vacuo
  21. customthe residue was partitioned between ethyl acetate
  22. customThe organic phase was separated
  23. dry with materialdried (Na2SO4)
  24. filtrationfiltered
  25. customevaporated in vacuo

Sources & evidence

ORD record
ord-f876386e67d041fe97da422c843d5c28
Source dataset
uspto-grants-2001_11
Patent number
US06313118B1

Reaction notes

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