Sodium Carbonate → 3-(Isoquinolin-4-yl)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene

HRID 1871917Notes

Reaction equation

HRID 1871917 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](B(O)O)=[CH:3][N:2]=1.FC(F)(F)S(O[C:20]1[CH2:26][CH:25]2[N:27]([CH3:28])[CH:22]([CH2:23][CH2:24]2)[CH:21]=1)(=O)=O.[Cl-].[Li+].C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.CO>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:20]2[CH2:21][CH:22]3[N:27]([CH3:28])[CH:25]([CH2:24][CH2:23]3)[CH:26]=2)=[CH:3][N:2]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 3761204Isoquinoline-4-boronic acidHCID 11993054(-)-8-methyl-3-(trifluoromethylsulfonyloxy)-8-aza-bicyclo[3.2.1]oct-2-ene

Product 1

HCID 186899123-(Isoquinolin-4-yl)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranCatalystHCID 887MethanolSolvent

Procedure

A mixture of isoquinolin-4-ylboronic acid, 3-trifluoromethanesulfonyloxy-8-methyl-8-azabicyclo [3.2.1]-oct-2-ene, lithium chloride, [1,1'-bis(diphenylphos-phino)-1-ferrocene]-palladium II chloride, and 2M aqueous sodium carbonate in tetrahydrofuran containing a few drops of methanol is stirred at reflux for about 4 hours. The reaction is cooled to room temperature and then partitioned between ethyl acetate and 2N sodium hydroxide. The phases are separated and the aqueous phase extracted well with ethyl acetate. The organic phases are combined, washed with saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure. The residue is subjected to flash silica gel chromatography. Fractions containing product are combined and concentrated under reduced pressure to provide 3-(isoquinolin-4-yl)-8-methyl-8-azabicyclo[3.2.1]oct-2-ene.

Workup

  1. temperatureat reflux for about 4 hours
  2. custompartitioned between ethyl acetate and 2N sodium hydroxide
  3. customThe phases are separated
  4. extractionthe aqueous phase extracted well with ethyl acetate
  5. washwashed with saturated aqueous sodium chloride
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. additionFractions containing product
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-590fc67172d3422b869eacce6c45cc30
Source dataset
uspto-grants-2000_08
Patent number
US06107307

Reaction notes

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