Thiophene → Ethyl (E)-4-[2-(5,5-dimethyl-8-(2-thienyl)-5,6-dihydronaphthalen-2-yl)ethenyl]-benzoate

HRID 2085836Notes

Reaction equation

HRID 2085836 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.C([Li:10])CCC.[CH3:11][C:12]1([CH3:43])[CH2:21][CH:20]=[C:19](OS(C(F)(F)F)(=O)=O)[C:18]2[CH:17]=[C:16](/[CH:30]=[CH:31]/[C:32]3[CH:42]=[CH:41][C:35]([C:36]([O:38][CH2:39][CH3:40])=[O:37])=[CH:34][CH:33]=3)[CH:15]=[CH:14][C:13]1=2>O1CCCC1.[Cl-].[Zn+2].[Cl-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Li:10][C:2]1[S:1][CH:5]=[CH:4][CH:3]=1.[CH3:43][C:12]1([CH3:11])[CH2:21][CH:20]=[C:19]([C:2]2[S:1][CH:5]=[CH:4][CH:3]=2)[C:18]2[CH:17]=[C:16](/[CH:30]=[CH:31]/[C:32]3[CH:33]=[CH:34][C:35]([C:36]([O:38][CH2:39][CH3:40])=[O:37])=[CH:41][CH:42]=3)[CH:15]=[CH:14][C:13]1=2

Participants

8

Reactant 3

HCID 8030ThiopheneHCID 19695065ethyl (E)-4-[2-(5,5-dimethyl-8-(trifluoromethylsulfonyl)oxy-5,6-dihydronaphthalen-2-yl)ethenyl]benzoate2×HCID 178418339Butyllithium

Product 2

HCID 15887383Ethyl (E)-4-[2-(5,5-dimethyl-8-(2-thienyl)-5,6-dihydronaphthalen-2-yl)ethenyl]-benzoateHCID 178418439HCID 178418439, compound

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

A solution of lithiothiophene was prepared by the addition of 0.10 g (0.095 mL, 1.2 mmol) of thiophene to a cold solution (−78° C.) of 0.61 g (0.90 mL, 1.4 mmol, 1.6 M in hexanes) of n-butyl lithium in 2.0 mL of tetrahydrofuran. The solution was stirred at −78° C. for 35 min and then a solution of 0.158 g (1.2 mmol) of zinc chloride in 2.0 mL of tetrahydrofuran was added. The resulting solution was stirred at −78° C. to room temperature for 1 h and then the organozinc was added via cannula to a mixture of 0.212 g (0.44 mmol) of ethyl (E)-4-[2-(5,5-dimethyl-8-(trifluoromethylsulfonyl)oxy-5,6dihydronaphthalen-2-yl)ethenyl]benzoate (Compound A9) and 18 mg (0.016 mmol) of tetrakis(triphenylphosphine)palladium(0) in 2.0 mL of tetrahydrofuran. The resulting mixture was stirred at room temperature for 10 min and then heated at 50° C. for 1 h. The reaction was quenched by the addition of sat. aqueous NH4Cl. The mixture was extracted with EtOAc (2×), and washed with brine. The organic phase was dried over Na2SO4 and then concentrated in vacuo. The crude material product was purified by flash chromatography (silica, 15% ethyl acetate in hexanes) to afford the title compound as a solid.

Workup

  1. stirringThe resulting solution was stirred at −78° C. to room temperature for 1 h
  2. stirringThe resulting mixture was stirred at room temperature for 10 min
  3. temperatureheated at 50° C. for 1 h
  4. customThe reaction was quenched by the addition of sat. aqueous NH4Cl
  5. extractionThe mixture was extracted with EtOAc (2×)
  6. washwashed with brine
  7. dry with materialThe organic phase was dried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe crude material product was purified by flash chromatography (silica, 15% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-b47a9c0e4fd7432596387cf0e0d9b571
Source dataset
uspto-grants-2004_04
Patent number
US06720425B2

Reaction notes

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