p-Toluenesulfonic acid → HCID 60151763, compound

HRID 2404606Notes

Reaction equation

HRID 2404606 reaction equation
CC1C=CC(S(O)(=O)=O)=CC=1.[CH3:12][N:13]([CH2:15][CH:16]1[C:22]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([OH:30])[CH:25]=2)(O)[CH2:21][CH:20]2[CH2:31][CH:17]1[CH2:18][CH2:19]2)[CH3:14].C([O-])([O-])=O.[K+].[K+]>C1(C)C=CC=CC=1>[CH3:14][N:13]([CH2:15][CH:16]1[CH:17]2[CH2:31][CH:20]([CH2:19][CH2:18]2)[CH:21]=[C:22]1[C:24]1[CH:25]=[C:26]([OH:30])[CH:27]=[CH:28][CH:29]=1)[CH3:12].[CH3:14][N:13]([CH2:15][C:16]1[CH:17]2[CH2:31][CH:20]([CH2:21][C:22]=1[C:24]1[CH:25]=[C:26]([OH:30])[CH:27]=[CH:28][CH:29]=1)[CH2:19][CH2:18]2)[CH3:12]

Participants

6

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 11430Potassium CarbonateHCID 60152584HCID 60152584, compound

Product 2

HCID 60151763HCID 60151763, compoundYield 50.2%HCID 68291602HCID 68291602, compoundYield 11.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Add TsOH (5.0 g, 29.1 mmol) to a solution of 2-dimethylaminomethyl-3-(3-hydroxy-phenyl)-bicyclo[3.2.1]octan-3-ol (4.8 g, 17.5 mmol) in toluene (150 mL). Heat the reaction mixture to reflux for 2 hours and then quench the reaction by addition of saturated aqueous K2CO3 (20 mL). Extract the aqueous layer with EtOAc (60 mL×3). The combined organic layers are washed with brine, dried over Na2SO4 and evaporated under vacuum. Purify the residue by preparative HPLC to yield 3-(4-dimethylaminomethyl-bicyclo[3.2.1]oct-2-en-3-yl)-phenol (2.27 g, 50.2%; MS (m/z): 258 (M+1)) and 3-(2-((dimethylamino)methyl)bicyclo[3.2.1]oct-2-en-3-yl)phenol (517 mg, 11.5%; MS (m/z): 258 (M+1)) as white solid. Two isomers show comparable biological activity in bioassay.

Workup

  1. temperatureHeat the reaction mixture
  2. temperatureto reflux for 2 hours
  3. customquench
  4. customthe reaction
  5. extractionExtract the aqueous layer with EtOAc (60 mL×3)
  6. washThe combined organic layers are washed with brine
  7. dry with materialdried over Na2SO4
  8. customevaporated under vacuum
  9. customPurify the residue by preparative HPLC

Sources & evidence

ORD record
ord-a8dc7a6fd51949cea60828599beb51b7
Source dataset
uspto-grants-2014_08
Patent number
US08802728B2

Reaction notes

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