Hydrochloric Acid → 2-t-Butyldimethylsilyl-3-formyl-6-methoxybenzofuran

HRID 1191978Notes

Reaction equation

HRID 1191978 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:26][CH3:27])=[CH:25][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[CH:25]=[C:24]([O:26][CH3:27])[CH:23]=[CH:22][C:11]=2[C:12]=1[CH:13]=[O:14])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 67287841HCID 67287841, compound

Product 1

HCID 574219572-t-Butyldimethylsilyl-3-formyl-6-methoxybenzofuran

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 2-t-butyldimethylsilyl-3-(t-butyldimethylsilyloxymethylene)-6-methoxy-benzofuran (1.09 g, 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); 1H NMR (300 MHz, CDCl3) δ 7.57 (d, 1H, J=8.57 Hz), 7.00 (d, 1H, J=2.17 Hz), 6.86 (dd, 1H, J=8.55, 2.22 Hz), 4.81 (s, 2H, CH2), 3.84 (s, 3H, OMe), 0.94 (s, 9H), 0.37 (s, 6H). The crude yellow paste (˜985 mg) 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 which crystallized on standing (485 mg, 68%); 1H NMR (300 MHz, CDCl3) δ 10.25 (s, 1H, CHO), 8.06 (d, 1H, J=8.61 Hz), 7.03 (d, 1H, J=2.16 Hz), 6.95 (dd, 1H, J=8.60, 2.19 Hz), 3.84 (s, 3H, OMe), 0.97 (s, 9H), 0.46 (s, 6H); 13C NMR (75 MHz, CDCl3) δ 186.91 (CHO), 174.18, 159.19, 159.17, 132.82, 122.77, 117.34, 113.56, 95.36, 55.60, 27.04, 17.09, −5.24.

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 yellow paste (˜985 mg) 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-57898eb48b1f45e28ddc97a86c5f002f
Source dataset
uspto-grants-2014_03
Patent number
US08680135B2

Reaction notes

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