Propyne → 6-Methoxy-2-methylbenzofuran

HRID 250259Notes

Reaction equation

HRID 250259 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. 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 and stirred for 2 days. The reaction mixture is quenched with water (800 mL) and extracted with EtOAc (500 mL). The organic layers are dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product is purified via flash chromatography eluting with 10% EtOAc/Hexanes. The appropriate fractions are concentrated. The material is dried in vacuo to afford the title compound (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. stirringstirred 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 are dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product is purified via flash chromatography
  9. washeluting with 10% EtOAc/Hexanes
  10. concentrationThe appropriate fractions are concentrated
  11. customThe material is dried in vacuo

Sources & evidence

ORD record
ord-e8cc3ca01a9f4d909a77703d9228ccc7
Source dataset
uspto-grants-2011_01
Patent number
US07863302B2

Reaction notes

Loading…