8-Methyl-8-azabicyclo(3.2.1)octan-3-ol → 6-(8-Methyl-8-aza-bicyclo[3.2.1]oct-3-yloxy)-isoquinoline

HRID 1621285Notes

Reaction equation

HRID 1621285 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.[OH:32][C:33]1[CH:34]=[C:35]2[C:40](=[CH:41][CH:42]=1)[CH:39]=[N:38][CH:37]=[CH:36]2.[CH3:43][N:44]1[CH:48]2[CH2:49][CH:50](O)[CH2:51][CH:45]1[CH2:46][CH2:47]2>ClCCl.C(N(CC)CC)C>[CH3:43][N:44]1[CH:48]2[CH2:47][CH2:46][CH:45]1[CH2:51][CH:50]([O:32][C:33]1[CH:34]=[C:35]3[C:40](=[CH:41][CH:42]=1)[CH:39]=[N:38][CH:37]=[CH:36]3)[CH2:49]2

Participants

7

Reactant 4

HCID 84248-Methyl-8-azabicyclo(3.2.1)octan-3-olHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 135483582Isoquinolin-6-ol

Product 1

HCID 251091096-(8-Methyl-8-aza-bicyclo[3.2.1]oct-3-yloxy)-isoquinolineYield 18%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

625 mg of triphenyl phosphine were dissolved in 20 mL of dry dichloromethane, 0.095 mL of diethyl azodicarboxylate were added and the solution was shaken for 20 minutes. 69 μL of triethyl amine, 72.6 mg of 6-hydroxy isoquinoline and 67.1 mg of tropine were added and the mixture was shaken overnight. The reaction mixture was filtered, the remainders washed thoroughly with dichloromethane and the combined organic layer was extracted twice with 1N sodium hydroxide and water, respectively. The organic layer was dried, evaporated to dryness and the crude material was purified by HPLC. The product was dissolved in 2N HCl and lyophilized to give 23 mg of 6-(8-Methyl-8-aza-bicyclo[3.2.1]oct-3-yloxy)-isoquinoline (52) as the hydrochloride. Rt=0.52 min (Method A). Detected mass: 269.2 (M+H+).

Workup

  1. stirringthe mixture was shaken overnight
  2. filtrationThe reaction mixture was filtered
  3. washthe remainders washed thoroughly with dichloromethane
  4. extractionthe combined organic layer was extracted twice with 1N sodium hydroxide and water
  5. customThe organic layer was dried
  6. customevaporated to dryness
  7. customthe crude material was purified by HPLC
  8. dissolutionThe product was dissolved in 2N HCl

Sources & evidence

ORD record
ord-e6d3c5c7cc48486e9bb3a2aa0cc659b9
Source dataset
uspto-grants-2014_07
Patent number
US08772492B2

Reaction notes

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