Ethyl Acetate → Ethyl 2-(5-methoxy-2,3-dihydro-1H-inden-1-yl)acetate

HRID 1508472Notes

Reaction equation

HRID 1508472 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[C:10](=O)[CH2:9][CH2:8]2.[C:15]([O:18][CH2:19][CH3:20])(=[O:17])[CH3:16]>C1COCC1>[CH3:3][O:4][C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[CH:10]([CH2:16][C:15]([O:18][CH2:19][CH3:20])=[O:17])[CH2:9][CH2:8]2

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 787875-Methoxyindan-1-one

Product 1

HCID 10263432Ethyl 2-(5-methoxy-2,3-dihydro-1H-inden-1-yl)acetate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

An oven dried flask was charged with sodium hydride (60 wt %) (173 mg, 4.32 mmol) and THF (15 mL) and cooled to 0° C. Triethyl phosphonoacetate (0.864 mL, 4.32 mmol) was added dropwise and the reaction was then heated to 50° C. for 1 hr. The reaction was then cooled to 0° C., and 5-methoxy-1-indanone (500 mg, 3.08 mmol) was added via cannula in THF (3×5 mL). The reaction was then refluxed for 17 hours. Next, the reaction was cooled to room temperature and diluted with ethyl acetate (50 mL). The organic layer was washed with water (2×50 mL) and brine (50 mL), dried over sodium sulfate, filtered, and concentrated. The residue was dissolved in ethanol (15 mL) and 10% palladium on carbon (150 mg) was added. The reaction was stirred at room temperature under an atmosphere of hydrogen (balloon) for 17 hours. At this point, the catalyst was removed by filtration, and the filtrate was concentrated. Purification of the residue via flash chromatography on silica gel (0 to 40% ethyl acetate/hexanes) afforded ethyl (5-methoxy-2,3-dihydro-1H-inden-1-yl)acetate. 1H NMR (CDCl3, 500 MHz) δ 7.07 (d, J=8.5 Hz, 1H), 6.78 (s, 1H), 6.71 (dd, J=8.2, 2.3 Hz, 1H), 4.18 (m, 2H), 3.78 (s, 3H), 3.53 (m, 1H), 2.95-2.65 (m, 3H), 2.45-2.30 (m, 2H), 1.76 (m, 1H), 1.28 (t, J=7.2 Hz, 3H).

Workup

  1. customAn oven dried flask
  2. temperaturethe reaction was then heated to 50° C. for 1 hr
  3. temperatureThe reaction was then cooled to 0° C.
  4. temperatureThe reaction was then refluxed for 17 hours
  5. temperatureNext, the reaction was cooled to room temperature
  6. washThe organic layer was washed with water (2×50 mL) and brine (50 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. dissolutionThe residue was dissolved in ethanol (15 mL)
  11. addition10% palladium on carbon (150 mg) was added
  12. customAt this point, the catalyst was removed by filtration
  13. concentrationthe filtrate was concentrated
  14. customPurification of the residue via flash chromatography on silica gel (0 to 40% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-2d8dd0a203e249b1ae67cd4da1833cfe
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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