Sodium Chloride → 4-Methoxy-5-(5,6,7,8-tetrahydronaphthalen-2-yl)thiophene-3-carbonitrile

HRID 337369Notes

Reaction equation

HRID 337369 reaction equation
Br[C:2]1[S:6][CH:5]=[C:4]([C:7]#[N:8])[C:3]=1[O:9][CH3:10].[CH:11]1[C:20]2[CH2:19][CH2:18][CH2:17][CH2:16][C:15]=2[CH:14]=[CH:13][C:12]=1B(O)O.C(=O)([O-])[O-].[K+].[K+].[Cl-].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C.O.COCCOC>[CH3:10][O:9][C:3]1[C:4]([C:7]#[N:8])=[CH:5][S:6][C:2]=1[C:13]1[CH:12]=[CH:11][C:20]2[CH2:19][CH2:18][CH2:17][CH2:16][C:15]=2[CH:14]=1

Participants

10

Reactant 4

HCID 5234Sodium ChlorideHCID 11430Potassium CarbonateHCID 22184118(5,6,7,8-Tetrahydronaphthalen-2-yl)boronic acid2×HCID 681634485-Bromo-4-metoxythiophene-3-carbonitrile

Product 1

HCID 681614114-Methoxy-5-(5,6,7,8-tetrahydronaphthalen-2-yl)thiophene-3-carbonitrileYield 82%

Reagents, catalysts & solvents 5

HCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

3.53 g of 5-bromo-4-metoxythiophene-3-carbonitrile synthesized in accordance with WO2006062247, 3.13 g of 5,6,7,8-tetrahydronaphthalen-2-yl boronic acid synthesized above in (3), 0.21 g of palladium acetate, 6.70 g of anhydrous potassium carbonate and 5.10 g of tetrabutylammonium bromide were mixed with 30 ml of 1,2-dimethoxyethane and 30 ml of water and allowed to react at room temperature for 19 hours with stirring. After addition of 200 ml of ethyl acetate and 150 ml of saturated aqueous sodium chloride, the reaction mixture was stirred at room temperature for 1 hour. The precipitated black solid was removed by suction filtration (through Celite). The filtrate was allowed to separate, and the ethyl acetate layer was withdrawn, washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=1/15) to obtain 3.56 g of the desired product (yield 82%).

Workup

  1. customto react at room temperature for 19 hours
  2. stirringthe reaction mixture was stirred at room temperature for 1 hour
  3. customThe precipitated black solid was removed by suction filtration (through Celite)
  4. customto separate
  5. customthe ethyl acetate layer was withdrawn
  6. washwashed with saturated aqueous sodium chloride
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=1/15)

Sources & evidence

ORD record
ord-83c45ec3538e4216895db9963d915f6a
Source dataset
uspto-grants-2014_11
Patent number
US08889732B2

Reaction notes

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