Methyl iodide → (3-Methoxy-5-oxo-5,6,7,8-tetrahydro-naphthalen-1-yloxy)-acetic acid tert-butyl ester

HRID 2384005Notes

Reaction equation

HRID 2384005 reaction equation
[C:1]([O:5][C:6](=[O:21])[CH2:7][O:8][C:9]1[C:18]2[CH2:17][CH2:16][CH2:15][C:14](=[O:19])[C:13]=2[CH:12]=[C:11]([OH:20])[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[C:22](=O)([O-])[O-].[K+].[K+].IC>CC(C)=O.CN(C=O)C.O.[Cl-].[Na+].O>[C:1]([O:5][C:6](=[O:21])[CH2:7][O:8][C:9]1[C:18]2[CH2:17][CH2:16][CH2:15][C:14](=[O:19])[C:13]=2[CH:12]=[C:11]([O:20][CH3:22])[CH:10]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 59192505(3-Hydroxy-5-oxo-5,6,7,8-tetrahydro-naphthalen-1-yloxy)-acetic acid tert-butyl ester

Product 1

HCID 59192503(3-Methoxy-5-oxo-5,6,7,8-tetrahydro-naphthalen-1-yloxy)-acetic acid tert-butyl esterYield 94%

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a suspension of (3-hydroxy-5-oxo-5,6,7,8-tetrahydro-naphthalen-1-yloxy)-acetic acid tert-butyl ester (XXX, 78 mg, 0.27 mmol) and potassium carbonate (111 mg, 0.8 mmol) in acetone (4 mL) and DMF (2 mL) was added iodomethane (114 mg, 0.8 mmol) at room temperature under nitrogen. The resulting red-brown suspension was heated at reflux for 2 days. The reaction mixture was then cooled to room temperature and diluted with water (10 mL) and brine (10 mL). The resulting mixture was extracted with ethyl acetate (2×35 mL). The combined organic extracts were washed with brine (50 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The crude product was purified by using ISCO (40 g) column chromatography (gradient elution with 5-40% ethyl acetate in hexanes) to obtain (3-methoxy-5-oxo-5,6,7,8-tetrahydro-naphthalen-1-yloxy)-acetic acid tert-butyl ester (76 mg, 94%) as a light yellow solid: ES(+)-HRMS m/e calcd. for C17H22O5 (M+H)+307.1540, obsd. 307.1540.

Workup

  1. temperatureThe resulting red-brown suspension was heated
  2. temperatureat reflux for 2 days
  3. extractionThe resulting mixture was extracted with ethyl acetate (2×35 mL)
  4. washThe combined organic extracts were washed with brine (50 mL)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified
  9. washISCO (40 g) column chromatography (gradient elution with 5-40% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-6ef54e0253204e299bd6400df42be772
Source dataset
uspto-grants-2012_09
Patent number
US08263656B2

Reaction notes

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