Thiophene → Methyl 5,5-dimethyl-5,6-dihydro-8-(2-thienyl)-2-naphthalenecarboxylate

HRID 481223Notes

Reaction equation

HRID 481223 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.C([Li])CCC.[CH3:11][C:12]1([CH3:34])[CH2:21][CH:20]=[C:19](OS(C(F)(F)F)(=O)=O)[C:18]2[CH:17]=[C:16]([C:30]([O:32][CH3:33])=[O:31])[CH:15]=[CH:14][C:13]1=2>C1COCC1.[Cl-].[Cl-].[Zn+2]>[CH3:11][C:12]1([CH3:34])[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]([C:30]([O:32][CH3:33])=[O:31])[CH:15]=[CH:14][C:13]1=2

Participants

6

Reactant 3

HCID 8030ThiopheneHCID 10570750Methyl 5,5-dimethyl-5,6-dihydro-8-(trifluoromethylsulfonyl)oxy-naphthalene-2-carboxylate2×HCID 178418339Butyllithium

Product 1

HCID 10494326Methyl 5,5-dimethyl-5,6-dihydro-8-(2-thienyl)-2-naphthalenecarboxylate

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of 329.0 mg (3.93 mmol) of thiophene in 2.0 mL THF at 0° C. was added 251.8 mg (3.93 mmol, 1.56 mL of 2.5 M solution in hexanes) of n-butyllithium. After stirring for 3 h at 0° C., a solution of 845.0 mg (6.28 mmol) of ZnCl2 in 5.0 mL THF was added and the resulting solution stirred for 30 minutes. This solution was added to a second flask containing 570.0 mg (1.57 mmol) of methyl 5,5-dimethyl-5,6-dihydro-8-(trifluoromethylsulfonyl)oxy-naphthalene-2-carboxylate (Compound E4) and 76.0 mg (0.063 mmol) of tetrakis(triphenyphosphine)palladium(0) in 4.0 mL THF, and the resulting solution was heated to 50° C. for 3 h. Upon cooling to room temperature the reaction was quenched by the addition of saturated aqueous NH4Cl. Extraction with EtOAc was followed by washing of the combined organic layers with H2O and saturated aqueous NaCl, and drying over MgSO4. The dry solution was concentrated under reduced pressure and the title compound was isolated from the residue as a yellow oil by column chromatography (5-10% EtOAc/hexanes).

Workup

  1. stirringthe resulting solution stirred for 30 minutes
  2. additionThis solution was added to a second flask
  3. temperaturethe resulting solution was heated to 50° C. for 3 h
  4. temperatureUpon cooling to room temperature the reaction
  5. customwas quenched by the addition of saturated aqueous NH4Cl
  6. extractionExtraction with EtOAc
  7. washby washing of the combined organic layers with H2O and saturated aqueous NaCl
  8. dry with materialdrying over MgSO4
  9. concentrationThe dry solution was concentrated under reduced pressure

Sources & evidence

ORD record
ord-948d355b600c4d7dabaae2bc489c347a
Source dataset
uspto-grants-2003_11
Patent number
US06653483B1

Reaction notes

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