Ethyl bromoacetate → 5,8-Dimethoxy-1,2,3,4-tetrahydro-2-hydroxy-2-naphthaleneacetic acid

HRID 2118765Notes

Reaction equation

HRID 2118765 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[C:9]2[C:4]=1[CH2:5][CH2:6][C:7](=[O:15])[CH2:8]2.Br[CH2:17][C:18]([O:20]CC)=[O:19]>C1(C)C=CC=CC=1.C1C=CC=CC=1.[Zn]>[CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[C:9]2[C:4]=1[CH2:5][CH2:6][C:7]([OH:15])([CH2:17][C:18]([OH:20])=[O:19])[CH2:8]2

Participants

5

Reactant 2

HCID 7748Ethyl bromoacetateHCID 995955,8-Dimethoxy-2-tetralone

Product 1

HCID 201931955,8-Dimethoxy-1,2,3,4-tetrahydro-2-hydroxy-2-naphthaleneacetic acid

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 160055Benzene, mixed with toluene, dealkylation productSolvent

Procedure

A fifth of a solution of 20.6 g of 3,4-dihydro-5,8-dimethoxy-2(1H)-naphthalenone and 18.4 g of ethyl bromoacetate in 100 ml of toluene/benzene (1:1) was added to 7.4 g of activated zinc dust. An exothermic reaction set in after heating to reflux for a few minutes. The remainder of the solution was then added dropwise within 10 minutes. The reaction mixture was then heated to reflux for 11/2 hours, cooled and partitioned between 300 ml of benzene and 300 ml of 3N aqueous sulfuric acid. The organic phase was washed with water and saturated aqueous sodium bicarbonate solution and evaporated. The residue was dissolved in 200 ml of methanol, treated with a solution of 10 g of sodium hydroxide in 100 ml of water and the mixture was heated to reflux for 3 hours. The solution was concentrated to half of the volume, treated with 500 ml of water and the neutral constituents were extracted with 500 ml of chloroform. The aqueous phase was made acid with sulfuric acid and the product was extracted in 900 ml of ether. The extract was dried over magnesium sulfate and evaporated. Recrystallization of the residue yielded 5,8-dimethoxy-1,2,3,4-tetrahydro-2-hydroxy-2-naphthaleneacetic acid, m.p. 112°-114°.

Workup

  1. customAn exothermic reaction
  2. temperaturein after heating
  3. temperatureto reflux for a few minutes
  4. additionThe remainder of the solution was then added dropwise within 10 minutes
  5. temperatureThe reaction mixture was then heated
  6. temperatureto reflux for 11/2 hours
  7. temperaturecooled
  8. custompartitioned between 300 ml of benzene and 300 ml of 3N aqueous sulfuric acid
  9. washThe organic phase was washed with water and saturated aqueous sodium bicarbonate solution
  10. customevaporated
  11. dissolutionThe residue was dissolved in 200 ml of methanol
  12. additiontreated with a solution of 10 g of sodium hydroxide in 100 ml of water
  13. temperaturethe mixture was heated
  14. temperatureto reflux for 3 hours
  15. concentrationThe solution was concentrated to half of the volume
  16. additiontreated with 500 ml of water
  17. extractionthe neutral constituents were extracted with 500 ml of chloroform
  18. extractionthe product was extracted in 900 ml of ether
  19. dry with materialThe extract was dried over magnesium sulfate
  20. customevaporated
  21. customRecrystallization of the residue

Sources & evidence

ORD record
ord-1a3051ab578e42a6bedea37b095b99d6
Source dataset
uspto-grants-1987_07
Patent number
US04680310

Reaction notes

Loading…