1,2,3,4-Tetrahydroquinoline → 1-[(4-Pyridin-3-yl-8-azabicyclo[3.2.1]oct-8-yl)carbonyl]-1,2,3,4-tetrahydroquinoline

HRID 599354Notes

Reaction equation

HRID 599354 reaction equation
[NH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.ClC(Cl)(O[C:15](=[O:21])OC(Cl)(Cl)Cl)Cl.Cl.Cl.N1C=CC([CH:31]2[CH2:37][CH:36]3[NH:38][CH:33]([CH2:34][CH2:35]3)[CH2:32]2)=CC=1.C(=O)([O-])O.[Na+]>C(N(CC)CC)C.ClCCl>[N:1]1[CH:10]=[CH:5][CH:4]=[C:3]([CH:37]2[CH:36]3[N:38]([C:15]([N:1]4[C:10]5[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=5)[CH2:4][CH2:3][CH2:2]4)=[O:21])[CH:33]([CH2:34][CH2:35]3)[CH2:32][CH2:31]2)[CH:2]=1

Participants

7

Reactant 4

HCID 694601,2,3,4-TetrahydroquinolineHCID 94429TriphosgeneHCID 516892Sodium BicarbonateHCID 672677423-Pyridin-4-yl-8-azabicyclo[3.2.1]octane dihydrochloride

Product 1

HCID 249616021-[(4-Pyridin-3-yl-8-azabicyclo[3.2.1]oct-8-yl)carbonyl]-1,2,3,4-tetrahydroquinolineYield 19.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent2×

Procedure

0.241 g of 1,2,3,4-tetrahydroquinoline, 20 ml of dichloromethane and 0.24 ml of triethylamine are placed in a 50 ml round-bottomed flask under a nitrogen atmosphere. 0.178 g of triphosgene is added at 0° C. and then the reaction mixture is left to stir at ambient temperature for 3 h. 0.34 g of 3-pyridin-4-yl-8-azabicyclo[3.2.1]octane dihydrochloride and 1.19 ml of triethylamine are subsequently added and the reaction mixture is then refluxed for three hours. 200 ml of a saturated aqueous solution of sodium hydrogen carbonate are added and the aqueous phase is then extracted three times with dichloromethane. The organic phases are combined, dried over sodium sulfate and evaporated under reduced pressure. The residue is chromatographed on silica gel with a 9/1 mixture of dichloromethane/methanol. 0.04 g of 1-[(4-pyridin-3-yl-8-azabicyclo[3.2.1]oct-8-yl)carbonyl]-1,2,3,4-tetrahydroquinoline is obtained.

Workup

  1. waitthe reaction mixture is left
  2. temperaturethe reaction mixture is then refluxed for three hours
  3. extractionthe aqueous phase is then extracted three times with dichloromethane
  4. dry with materialdried over sodium sulfate
  5. customevaporated under reduced pressure
  6. customThe residue is chromatographed on silica gel with a 9/1 mixture of dichloromethane/methanol

Sources & evidence

ORD record
ord-92cd74e0f83c4783921e5cd81f369fd9
Source dataset
uspto-grants-2011_03
Patent number
US07897773B2

Reaction notes

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