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

HRID 527652노트

반응식

HRID 527652 반응식
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

참가 물질

11

반응물 6

HCID 1118Sulfuric AcidHCID 3283Diethyl EtherHCID 6101p-Toluenesulfonic acidHCID 25517Ammonium ChlorideHCID 131242277-(methoxymethoxy)-3H-isobenzofuran-1-one2회HCID 178418573HCID 178418573, 화합물

생성물 1

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

시약·촉매·용매 4

HCID 887Methanol용매HCID 6342Acetonitrile용매2회HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

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온도
-70 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-fc048f22957a4ea091d8eac92f168bd0
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346790B2

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