Hydrochloric Acid → 2-t-Butyldimethylsilyl-3-formyl-6-methoxy-7-isopropoxybenzofuran

HRID 529236Notes

Reaction equation

HRID 529236 reaction equation
[Si:1]([CH:8]1[C:12](=[CH:13][O:14][Si](C(C)(C)C)(C)C)[C:11]2[CH:22]=[CH:23][C:24]([O:30][CH3:31])=[C:25]([O:26][CH:27]([CH3:29])[CH3:28])[C:10]=2[O:9]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Cl>CO>[Si:1]([C:8]1[O:9][C:10]2[C:25]([O:26][CH:27]([CH3:28])[CH3:29])=[C:24]([O:30][CH3:31])[CH:23]=[CH:22][C:11]=2[C:12]=1[CH:13]=[O:14])([C:4]([CH3:6])([CH3:7])[CH3:5])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 670422652-t-Butyldimethylsilyl-3-(t-butyldimethylsilyloxymethylene)-6-methoxy-7-isopropoxybenzofuran

Product 1

HCID 574219592-t-Butyldimethylsilyl-3-formyl-6-methoxy-7-isopropoxybenzofuranYield 53.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 2-t-butyldimethylsilyl-3-(t-butyldimethylsilyloxymethylene)-6-methoxy-7-isopropoxybenzofuran (2.69 mmol) in methanol (100 mL) was added concentrated hydrochloric acid (200 μL) and the reaction was stirred for 30 minutes (monitored by tlc), quenched with triethylamine (2 mL) and the solvent removed by distillation under vacuum. The residue was dissolved in dichloromethane (20 mL), washed with water (10 mL), dried over magnesium sulfate, concentrated under vacuum and co-distilled with toluene (20 mL). The crude product was dissolved in dry dichloromethane (4 mL) and added to a stirred solution of Collin's reagent (chromium trioxide (1.01 g), pyridine (1.65 mL) in dry dichloromethane (30 mL)). The suspension was stirred for 10 minutes, filtered and the residue washed with diethyl ether (20 mL). The filtrate was concentrated onto silica (10 g) and purified by flash chromatography (silica gel, eluent=hexane/diethyl-ether/triethylamine (90:9:1) to afford the title compound as a light yellow oil (503 mg, 48%); 1H NMR (300 MHz, CDCl3) δ 10.25 (s, 1H, CHO), 7.79 (d, 1H, J=8.45 Hz), 6.98 (d, 1H, J=8.46 Hz), 4.65 (m, 1H), 3.89 (s, 3H, OMe), 1.35 (d, 6H, J=6.17 Hz), 0.97 (s, 9H), 0.45 (s, 6H).

Workup

  1. customquenched with triethylamine (2 mL)
  2. customthe solvent removed by distillation under vacuum
  3. dissolutionThe residue was dissolved in dichloromethane (20 mL)
  4. washwashed with water (10 mL)
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under vacuum and co-distilled with toluene (20 mL)
  7. dissolutionThe crude product was dissolved in dry dichloromethane (4 mL)
  8. additionadded to a stirred solution of Collin's reagent (chromium trioxide (1.01 g), pyridine (1.65 mL) in dry dichloromethane (30 mL))
  9. stirringThe suspension was stirred for 10 minutes
  10. filtrationfiltered
  11. washthe residue washed with diethyl ether (20 mL)
  12. concentrationThe filtrate was concentrated onto silica (10 g)
  13. custompurified by flash chromatography (silica gel, eluent=hexane/diethyl-ether/triethylamine (90:9:1)

Sources & evidence

ORD record
ord-b1d884bfbda94ee28d1fc8e57e8dabc4
Source dataset
uspto-grants-2016_05
Patent number
US09346842B2

Reaction notes

Loading…