1-Cyclohexenyl trifluoromethanesulfonate → 6-Methoxy-2-(1-cyclohexenyl)benzo[b]thiophene

HRID 354081Notes

Reaction equation

HRID 354081 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[CH:10]=[CH:9][S:8][C:7]=2[CH:11]=1.[Li]CCCC.[C:17]1(OS(C(F)(F)F)(=O)=O)[CH2:22][CH2:21][CH2:20][CH2:19][CH:18]=1.[Cl-].[Li+]>C1COCC1.[Cl-].[Cl-].[Zn+2].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>[C:17]1([C:9]2[S:8][C:7]3[CH:11]=[C:3]([O:2][CH3:1])[CH:4]=[CH:5][C:6]=3[CH:10]=2)[CH2:22][CH2:21][CH2:20][CH2:19][CH:18]=1

Participants

8

Reactant 4

HCID 3194401-Cyclohexenyl trifluoromethanesulfonateHCID 433294Lithium ChlorideHCID 136342376-Methoxy-1-benzothiopheneHCID 178418339Butyllithium

Product 1

HCID 235129036-Methoxy-2-(1-cyclohexenyl)benzo[b]thiopheneYield 68.1%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 6-methoxybenzo[b]thiophene (362 mg, 2.21 mmol) in 5.5 mL of THF at −20° C. was added dropwise 2.5 M nBuLi (0.97 mL, 2.4 mmol) and the reaction was stirred at 0° C. for 40 minutes and was then warmed to room temperature for 30 minutes. Next, ZnCl2 (390 mg, 2.87 mmol) in 2.5 mL of THF was added by cannula and the reaction was stirred at room temperature for 15 minutes. At this point, Pd(Ph3P)4 (102 mg), trifluoromethanesulfonic acid cyclohex-1-enyl ester (0.6 gm, 2.93 mmol)3 and anhydrous lithium chloride (0.28 gm, 6.63 mmol) were added and then the reaction mixture was stirred for 16 hrs. at room temperature. The tetrahydrofuran was removed in vacuo and the residue diluted with water and extracted with ethyl acetate. The combined organic layers was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was chromatographed on silica gel using hexanes as the eluant to yield 368 mg of the title compound.

Workup

  1. temperaturewas then warmed to room temperature for 30 minutes
  2. stirringthe reaction was stirred at room temperature for 15 minutes
  3. stirringthe reaction mixture was stirred for 16 hrs
  4. customat room temperature
  5. customThe tetrahydrofuran was removed in vacuo
  6. additionthe residue diluted with water
  7. extractionextracted with ethyl acetate
  8. dry with materialThe combined organic layers was dried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude product was chromatographed on silica gel

Sources & evidence

ORD record
ord-387e9b46e1da444aafb6a63060ec9a88
Source dataset
uspto-grants-2004_06
Patent number
US06756388B1

Reaction notes

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