Saccharin → 2-Methylbenzofuran-5-carbonitrile

HRID 717702Notes

Reaction equation

HRID 717702 reaction equation
S1([C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:5](=O)[NH:4]1)(=O)=O.[C:13]([Mg]Br)#[C:14][CH3:15].C1C[O:21]CC1>[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.[Cu]I>[CH3:15][C:14]1[O:21][C:10]2[CH:11]=[CH:12][C:7]([C:5]#[N:4])=[CH:8][C:9]=2[CH:13]=1

Participants

7

Reactant 3

HCID 5143SaccharinHCID 8028Tetrahydrofuran2×HCID 178419101HCID 178419101, compound

Product 1

HCID 136630382-Methylbenzofuran-5-carbonitrileYield 91%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalyst

Procedure

2-Iodo-4-cynophenol (0.25 g, 1 mmol) and saccharin (0.1 g) in HMDSA (2 ml) was refluxed for 2 h under N2, until the solution became clear. The solvent was distilled off under reduced pressure and the residue was dissolved in anhydrous THF (2 ml). This was added to a solution made by mixing anhydrous ZnCl2 (0.3 g; 2.2 mmol) with 0.5 M 1-propynyl magnesium bromide in THF (7.8 ml) in anhydrous THF (5 ml) at room temperature under N2. To it, Pd (PPh3)4 (0.15 g) was added at room temperature under N2 followed by catalytic amount of CuI. The mixture was stirred at room temperature for 3 h and quenched with saturated NH4Cl solution. The mixture was diluted to 50 ml with EtOAc and washed with H2O. The organic layer was separated, dried over MgSO4 and filtered. The filtrate was evaporated and the residue was dissolved in 1,4-dioxane (4 ml) and 1 M TBAF in THF (0.3 ml) was added and this was stirred for 4 h at reflux. The solvent was distilled off and the residue was purified by FCC (SiO2, hexane/EtOAc) to give the title compound (0.145 g, 91%), as colourless solid. 1H-NMR (CDCl3) 7.78 (s, 1H); 7.46-7.44 (m, 2H); 6.41 (bs, 1H); 2.47 (s, 3H).

Workup

  1. distillationThe solvent was distilled off under reduced pressure
  2. dissolutionthe residue was dissolved in anhydrous THF (2 ml)
  3. additionThis was added to a solution
  4. customquenched with saturated NH4Cl solution
  5. additionThe mixture was diluted to 50 ml with EtOAc
  6. washwashed with H2O
  7. customThe organic layer was separated
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customThe filtrate was evaporated
  11. dissolutionthe residue was dissolved in 1,4-dioxane (4 ml)
  12. addition1 M TBAF in THF (0.3 ml) was added
  13. stirringthis was stirred for 4 h
  14. temperatureat reflux
  15. distillationThe solvent was distilled off
  16. customthe residue was purified by FCC (SiO2, hexane/EtOAc)

Sources & evidence

ORD record
ord-40dfc2fb577d45859bbf227c7da213d1
Source dataset
uspto-grants-2015_11
Patent number
US09193716B2

Reaction notes

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