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

HRID 599348Notes

Reaction equation

HRID 599348 reaction equation
FC(F)(F)S(O[C:7]1[CH2:13][CH:12]2[NH:14][CH:9]([CH2:10][CH2:11]2)[CH:8]=1)(=O)=O.CC1(C)C(C)(C)OB([C:25]2[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=2)O1.[Cl-].[Li+].P([O-])([O-])([O-])=O.[K+].[K+].[K+].[O:42]1[CH2:47]COCC1>CN(C1C(C2[C-]=CC=CC=2)=CC=CC=1)C.C1[C@H]2CC(PC3[C@H]4C[C@H](CC4)C3)[C@H](C2)C1.Cl[Pd+].C(OCC)(=O)C.O>[N:27]1[CH:28]=[CH:29][CH:30]=[C:25]([C:7]2[CH2:13][CH:12]3[N:14]([C:47]([N:27]4[C:26]5[C:25](=[CH:13][CH:7]=[CH:8][CH:9]=5)[CH2:30][CH2:29][CH2:28]4)=[O:42])[CH:9]([CH2:10][CH2:11]3)[CH:8]=2)[CH:26]=1

Participants

9

Reactant 5

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 433294Lithium ChlorideHCID 27346563-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 866321818-Azabicyclo[3.2.1]oct-2-ene-3-yl trifluoromethanesulfonate

Product 1

HCID 248046411-[(3-Pyridin-3-yl-8-azabicyclo[3.2.1]oct-2-en-8-yl)carbonyl]-1,2,3,4-tetrahydroquinoline

Reagents, catalysts & solvents 3

HCID 11272965[(1R,4S)-2-Bicyclo[2.2.1]heptanyl]-[(1S,4R)-2-bicyclo[2.2.1]heptanyl]phosphane;chloropalladium(1+);N,N-dimethyl-2-phenylanilineCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

0.5 g of dihydroquinolin-1(2H)-ylcarbonyl)-8-azabicyclo[3.2.1]oct-2-ene-3-yl trifluoromethanesulfonate, 0.419 g of 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine, 0.1 g of lithium chloride, 0.765 g of potassium phosphate, 0.067 g of 2′-(dimethylamino)-2-biphenylpalladium(II)chloride dinorbornylphosphine and 4.3 ml of dioxane are introduced into a 10 ml glass tube. The tube is sealed, and then heated at 100° C. under microwave radiation for 50 minutes. Water and ethyl acetate are added. The aqueous phase is extracted three times with ethyl acetate. The organic phases are combined, dried over sodium sulfate and the solvent is evaporated off under reduced pressure. The residue is chromatographed on silica gel with a 3/7 mixture of heptane/ethyl acetate. 0.3 g of 1-[(3-pyridin-3-yl-8-azabicyclo[3.2.1]oct-2-en-8-yl)carbonyl]-1,2,3,4-tetrahydroquinoline is obtained.

Workup

  1. customThe tube is sealed
  2. extractionThe aqueous phase is extracted three times with ethyl acetate
  3. dry with materialdried over sodium sulfate
  4. customthe solvent is evaporated off under reduced pressure
  5. customThe residue is chromatographed on silica gel with a 3/7 mixture of heptane/ethyl acetate

Sources & evidence

ORD record
ord-d8ff008357d449e998e536870a537950
Source dataset
uspto-grants-2011_03
Patent number
US07897773B2

Reaction notes

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