Methanol → HCID 23512987, compound

HRID 354058Notes

Reaction equation

HRID 354058 reaction equation
S([CH2:11][N+:12]#[C-])(C1C=CC(C)=CC=1)(=O)=O.CC(C)([O-])C.[K+].[CH:20]([C:22]1[C:27]2[CH:28]=[CH:29][O:30][C:26]=2[C:25]([NH:31][S:32]([CH3:35])(=[O:34])=[O:33])=[CH:24][CH:23]=1)=O.CO>COCCOC>[C:11]([CH2:20][C:22]1[C:27]2[CH:28]=[CH:29][O:30][C:26]=2[C:25]([NH:31][S:32]([CH3:35])(=[O:34])=[O:33])=[CH:24][CH:23]=1)#[N:12]

Participants

6

Reactant 4

HCID 887MethanolHCID 161915Tosylmethyl isocyanideHCID 23512981HCID 23512981, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 23512987HCID 23512987, compoundYield 62.6%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent3×

Conditions

Temperature
-65 °C

Procedure

A solution of tosylmethyl isocyanide (1.8 g, 9.22 mmole) in anhydrous ethylene glycol dimethyl ether (60 mL) was added drop-wise into a stirred suspension of potassium tert-butoxide (2.81 g, 25.0 mmole) in anhydrous ethylene glycol dimethyl ether (60 mL) under nitrogen at −65° C. After stirring at −65° C. for 15 min., N-(4-formyl-benzofuran-7-yl)-methanesulfonamide (2.0 g, 8.36 mmole) in anhydrous ethylene glycol dimethyl ether (60 mL) was added drop-wise and the reaction temperature was maintained below −60° C. After stirring for another hour before methanol (30 mL) was added. The reaction mixture was heated to reflux for 20 minutes then stirred at room temperature for 16 hrs. The resulting solution was partitioned between ethyl acetate and aqueous 2% acetic acid. The organic extract was washed with brine, dried (anhydrous sodium sulfate) and concentrated under reduced pressure. The residue was purified by flash column chromatography over silica gel eluting with 40 to and 50% ethyl acetate in hexane to give N-(4-cyanomethyl-benzofuran-7-yl)-methanesulfonamide as a solid (1.31 g, 62%). 1H NMR (DMSO-d6) δ: 3.11 (s, 3H), 4.28 (s, 2H), 7.17 (d, 1H, J=2.2 Hz), 7.24-7.30 (m, 2H) 8.15 (d, 1H, J=2.2 Hz), 9.23 (s, 11H) M−H 249.

Workup

  1. temperaturethe reaction temperature was maintained below −60° C
  2. additionwas added
  3. temperatureThe reaction mixture was heated
  4. temperatureto reflux for 20 minutes
  5. stirringthen stirred at room temperature for 16 hrs
  6. customThe resulting solution was partitioned between ethyl acetate and aqueous 2% acetic acid
  7. extractionThe organic extract
  8. washwas washed with brine
  9. dry with materialdried (anhydrous sodium sulfate)
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by flash column chromatography over silica gel eluting with 40 to and 50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-418e5d4727534a5c98d0622f750ac033
Source dataset
uspto-grants-2004_06
Patent number
US06756395B2

Reaction notes

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