p-Toluenesulfonic acid → (trans)-N-benzyl-N-[3-(3,4-dimethoxyphenyl) cyclohexyl]amine

HRID 1108758Notes

Reaction equation

HRID 1108758 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]2[CH2:16][CH2:15][CH2:14][C:13](=O)[CH2:12]2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[CH2:18]([NH2:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1C=CC=CC=1>[CH2:18]([NH:25][C@H:13]1[CH2:14][CH2:15][CH2:16][C@H:11]([C:5]2[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=2)[CH2:12]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[CH2:18]([NH:25][C@H:13]1[CH2:14][CH2:15][CH2:16][C@@H:11]([C:5]2[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=2)[CH2:12]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

6

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 7504BenzylamineHCID 187841823-(3,4-Dimethoxyphenyl)cyclohexanone

Product 2

HCID 69971629(cis)-N-benzyl-N-[3-(3,4-dimethoxyphenyl)cyclohexyl]amineYield 32.4%HCID 69972634(trans)-N-benzyl-N-[3-(3,4-dimethoxyphenyl) cyclohexyl]amineYield 33.2%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

3-(3,4-Dimethoxyphenyl)cyclohexanone (6.90 g) and benzylamine (3.16 g) were refluxed for 1.5 hours in benzene (150 ml) in the presence of para-toluenesulfonic acid (630 mg), using a Dean-Stark apparatus while removing the water generated. After distilling off the benzene under reduced pressure, it was dissolved in methanol (120 ml) while cooling on ice, sodium borohydride (1.12 g) was gradually added and the mixture was stirred at room temperature for an hour. After concentrating the reaction solution, water was added, extraction was performed with chloroform, and the solution was washed with saturated sodium bicarbonate water and saturated saline. After drying with anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure to produce a light yellow oily substance which was then separated and purified by silica gel column chromatography (n-hexane:ethyl acetate=5:1→1:1→1:2), to give 3.16 g of (trans)-N-benzyl-N-[3-(3,4-dimethoxyphenyl) cyclohexyl]amine (33.2% yield) and 3.09 g of (cis)-N-benzyl-N-[3-(3,4-dimethoxyphenyl)cyclohexyl]amine (32.4% yield).

Workup

  1. customwhile removing the water
  2. distillationAfter distilling off the benzene under reduced pressure, it
  3. dissolutionwas dissolved in methanol (120 ml)
  4. temperaturewhile cooling on ice, sodium borohydride (1.12 g)
  5. additionwas gradually added
  6. concentrationAfter concentrating the reaction solution, water
  7. additionwas added
  8. extractionextraction
  9. washthe solution was washed with saturated sodium bicarbonate water and saturated saline
  10. dry with materialAfter drying with anhydrous magnesium sulfate
  11. distillationthe solvent was distilled off under reduced pressure
  12. customto produce a light yellow oily substance which
  13. customwas then separated
  14. custompurified by silica gel column chromatography (n-hexane:ethyl acetate=5:1→1:1→1:2)

Sources & evidence

ORD record
ord-f4b2a7408a74424a881dd804d49b961d
Source dataset
uspto-grants-2000_05
Patent number
US06069176

Reaction notes

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