Propyne → 6-Methoxy-2-methylbenzofuran

HRID 2261829Notes

Reaction equation

HRID 2261829 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[OH:10].[CH:11]#[C:12][CH3:13]>CN(C)C=O.CN(C)C(N(C)C)=N.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:9][O:8][C:5]1[CH:6]=[CH:7][C:2]2[CH:11]=[C:12]([CH3:13])[O:10][C:3]=2[CH:4]=1

Participants

7

Reactant 2

HCID 6335PropyneHCID 114140152-Iodo-5-methoxyphenol

Product 1

HCID 130130736-Methoxy-2-methylbenzofuranYield 69.2%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 664601,1,3,3-TetramethylguanidineSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 2-iodo-5-methoxy-phenol (39 g, 156 mmol) in dimethylformamide (300 mL) and N,N,N′,N′-tetramethylguanidine (150 mL) is treated with copper(I) Iodide (1.89 g, 9.82 mmol) and bis(triphenylphosphine)palladium(II) chloride (1.9 g; 2.71 mmol; 1.900 g). The mixture is cooled to −78° C., and propyne (100 g; 2.50 moles) is bubbled through the mixture for 1 hour. The reaction mixture is stirred and allowed to warm to room temperature gradually over 6 hours. After stirred for 2 days, the reaction mixture is quenched with water (800 mL) and extracted with EtOAc (500 mL). The organic layers is dried over Na2SO4, filtered and concentrated. The crude product is purified by flash chromatography (eluted with 10% EtOAc/Hexanes) and the appropriate fractions are concentrated. The material is dried in vacuo to afford 6-methoxy-2-methyl-benzofuran (17.5 g, 69%). 1H NMR (400 MHz, CDCl3): δ 7.31-7.29 (d, 1H), 6.95 (s, 1H), 6.81-6.79 (d, 1H), 6.26 (s, 1H), 3.81 (s, 3H), 2.40 (s, 3H).

Workup

  1. temperatureto warm to room temperature gradually over 6 hours
  2. stirringAfter stirred for 2 days
  3. customthe reaction mixture is quenched with water (800 mL)
  4. extractionextracted with EtOAc (500 mL)
  5. dry with materialThe organic layers is dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product is purified by flash chromatography (eluted with 10% EtOAc/Hexanes)
  9. concentrationthe appropriate fractions are concentrated
  10. customThe material is dried in vacuo

Sources & evidence

ORD record
ord-21162ec6c7b845829179e79b5d4c1ef8
Source dataset
uspto-grants-2010_12
Patent number
US07846960B2

Reaction notes

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