Sulfuric Acid → 3,3-dimethyl-1H-isobenzofuran-4-ol

HRID 527652Notes

Reaction equation

HRID 527652 reaction equation
COC[O:4][C:5]1[CH:6]=C[CH:8]=[C:9]2[C:13]=1C(=O)OC2.C[Mg]Br.[CH2:18]([O:20][CH2:21][CH3:22])[CH3:19].[Cl-].[NH4+].S(=O)(=O)(O)O.[C:30]1(C)C=CC(S(O)(=O)=O)=CC=1>C1COCC1.C(#N)C.CO.C(OCC)(=O)C>[CH3:19][C:18]1([CH3:30])[C:6]2[C:5]([OH:4])=[CH:13][CH:9]=[CH:8][C:22]=2[CH2:21][O:20]1

Participants

11

Reactant 6

HCID 1118Sulfuric AcidHCID 3283Diethyl EtherHCID 6101p-Toluenesulfonic acidHCID 25517Ammonium ChlorideHCID 131242277-(methoxymethoxy)-3H-isobenzofuran-1-one2×HCID 178418573HCID 178418573, compound

Product 1

HCID 685333883,3-dimethyl-1H-isobenzofuran-4-olYield 220.2%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-70 °C

Procedure

7-(methoxymethoxy)-3H-isobenzofuran-1-one (Intermediate 192, 550 mg, 2.8 mmol) was dissolved at −70° C. in dry THF (150 mL). A 3M solution of methylmagnesium bromide in diethyl ether (5.6 mL, 16.8 mmol) was added drop wise in 30 minutes and the obtained mixture stirred for 30 minutes at −70° C. and then 30 minutes at room temperature. The reaction mixture was poured into ethyl acetate (100 mL) and aqueous saturated solution of ammonium chloride (50 mL) at 0° C. The organic layer was collected, washed with an aqueous saturated solution of ammonium chloride (50 mL), brine (50 mL) and evaporated to give a yellow oil that was dissolved in acetonitrile (15 mL) and treated with sulphuric acid (0.15 mL). Acetonitrile was replaced with methyl alcohol (15 mL) and the resulting solution treated with p-toluenesulfonic acid (100 mg). The solution was heated to 60° C. and stirred for 2 hours. The solvent was evaporated and the residue dissolved in ethyl acetate (30 mL), washed twice with an aqueous saturated solution of sodium bicarbonate (10 mL) and then with an aqueous diluted solution of hydrochloric acid, dried over Na2SO4, and evaporated to dryness. The residue was purified by flash chromatography on silica gel using cyclohexane/ethyl acetate 90:10 as eluent affording the title compound (210 mg) as white solid.

Workup

  1. custom30 minutes
  2. customat room temperature
  3. customThe organic layer was collected
  4. washwashed with an aqueous saturated solution of ammonium chloride (50 mL), brine (50 mL)
  5. customevaporated
  6. customto give a yellow oil that
  7. temperatureThe solution was heated to 60° C.
  8. stirringstirred for 2 hours
  9. customThe solvent was evaporated
  10. dissolutionthe residue dissolved in ethyl acetate (30 mL)
  11. washwashed twice with an aqueous saturated solution of sodium bicarbonate (10 mL)
  12. dry with materialwith an aqueous diluted solution of hydrochloric acid, dried over Na2SO4
  13. customevaporated to dryness
  14. customThe residue was purified by flash chromatography on silica gel

Sources & evidence

ORD record
ord-fc048f22957a4ea091d8eac92f168bd0
Source dataset
uspto-grants-2016_05
Patent number
US09346790B2

Reaction notes

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