p-Toluenesulfonic acid → HCID 18784174, compound

HRID 1108750Notes

Reaction equation

HRID 1108750 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]2[CH2:14][CH2:13][CH2:12][C:11](=O)[CH2:10]2)[CH:6]=[CH:7][CH:8]=1.[CH2:16]([NH2:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1C=CC=CC=1>[CH2:16]([NH:23][CH:11]1[CH2:12][CH2:13][CH2:14][CH:9]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=2)[CH2:10]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 7504BenzylamineHCID 12039786HCID 12039786, compound

Product 1

HCID 18784174HCID 18784174, compoundYield 83.4%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

3-(3-Methoxyphenyl)cyclohexanone (13.1 g), benzylamine (6.88 g) and p-toluenesulfonic acid (1.22 g) were refluxed for 1.5 hours in benzene (200 ml) using a Dean-Stark apparatus while removing the water generated. After concentrating the reaction solution under reduced pressure, methanol (200 ml) was added and upon adding sodium borohydride (2.43 g) gradually under ice cooling, the mixture was stirred at room temperature for an hour. After concentrating the reaction solution under reduced pressure, water was added and extraction was performed with chloroform. The organic layer was washed with saturated aqueous solution of sodium bicarbonate and saturated saline, and then dried with anhydrous magnesium sulfate. The crude product obtained from distilling off the solvent under reduced pressure was separated and purified by silica gel column chromatography (n-hexane:ethyl acetate=5:1 to 1:1) to give 15.8 g of N-benzyl-N-[3-(3-methoxyphenyl) cyclohexyl]amine as a diastereomeric mixture (83.4% yield). Repeated silica gel column chromatography (n-hexane:ethyl acetate=5:1) allowed separation of the two diastereomers, with the trans form obtained from the earlier eluted fraction and the cis form obtained from the later eluted fraction.

Workup

  1. customwhile removing the water
  2. concentrationAfter concentrating the reaction solution under reduced pressure, methanol (200 ml)
  3. additionwas added
  4. additionupon adding sodium borohydride (2.43 g) gradually under ice cooling
  5. concentrationAfter concentrating the reaction solution under reduced pressure, water
  6. additionwas added
  7. extractionextraction
  8. washThe organic layer was washed with saturated aqueous solution of sodium bicarbonate and saturated saline
  9. dry with materialdried with anhydrous magnesium sulfate
  10. customThe crude product obtained
  11. distillationfrom distilling off the solvent under reduced pressure
  12. customwas separated
  13. custompurified by silica gel column chromatography (n-hexane:ethyl acetate=5:1 to 1:1)

Sources & evidence

ORD record
ord-3477bfcdbf464a2ab7e5b854ce348958
Source dataset
uspto-grants-2000_05
Patent number
US06069176

Reaction notes

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