Hydrochloric Acid → 6-Methoxy-1,2,3,4-tetrahydronaphthalen-2-one

HRID 2302008Notes

Reaction equation

HRID 2302008 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([O:13]C)[CH:9]=2)[CH:4]=1.[Na].Cl.O>CCO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH2:9][C:8](=[O:13])[CH2:7][CH2:6]2

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 962WaterHCID 796272,6-DimethoxynaphthaleneHCID 5360545Sodium2×

Product 1

HCID 755826-Methoxy-1,2,3,4-tetrahydronaphthalen-2-oneYield 125.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A suspension of 2,6-dimethoxynaphthalene (20.0 g, Aldrich) in 200 mL of anhydrous EtOH was heated to reflux under a stream of nitrogen. Sodium spheres (18 g, Aldrich) were added gradually to the hot suspension over a period of 2 hours. Additional ETOH (50 ml) was added and the reaction was heated until all of the sodium had dissolved. The solution was cooled to room temperature and placed in an ice bath. The addition of 6 N HCl brought the solution to pH 6, and additional HCl (10 mL) was added. The solution was heated to reflux for 0.5 h. The golden mixture was cooled to room temperature, H2O (200 mL) was added, and the solution was extracted with ET2O. The combined ET2O extracts were dried (Na2SO4), filtered, and concentrated to afford 6-methoxy-2-tetra-lone as a red oil (23.5 g). Triethyl phosphono-acetate (29 mL, Aldrich) was added dropwise to a suspension of hexane-washed sodium hydride (5.8 g of 60% dispersion) in benzene (80 mL) cooled in an ice bath. The phos-phonate solution was stirred at room temperature for 0.5 h, and the ice bath was replaced. A solution of 6-methoxy-2-tetralone (23.5 g) in benzene (20 mL) was added to the phosphonate solution over 10 minutes, and the reaction was allowed to stir at room temperature overnight. The reaction was poured into H2O and extracted with EtOAc (3×150 mL). The combined extracts were dried (Na2SO4), filtered, and concentrated to afford a brown oil which was purified using silica gel chromatography. Elution with 10% EtOAc/hexane afforded the title compound (27 g) as a yellow oil. NMR (300 MHz, CDCl3) δ6.98 (d, J=9.03 Hz, 1 H), 6.79-6.70 (m, 2H), 6.35 (s, 1H), 3.94 (q, J=7.11 Hz, 2H), 3.58 (s, 3H), 2.99 (s, 2H), 2.61 (t, J 8.11 Hz, 2H), 2.14 (t, J=8.07 Hz, 2H), 1.08 (t, J 7.14 Hz, 3H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux under a stream of nitrogen
  3. additionwere added gradually to the hot suspension over a period of 2 hours
  4. additionAdditional ETOH (50 ml) was added
  5. dissolutionhad dissolved
  6. customplaced in an ice bath
  7. additionwas added
  8. temperatureThe solution was heated
  9. temperatureto reflux for 0.5 h
  10. temperatureThe golden mixture was cooled to room temperature
  11. extractionthe solution was extracted with ET2O
  12. dry with materialThe combined ET2O extracts were dried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-ef0e9c0a72ee4ae2aabd54f1b18b3c2b
Source dataset
uspto-grants-2002_08
Patent number
US06429214B1

Reaction notes

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