Ethyl bromoacetate → 4-Oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid

Temperature

50 °C

100 mL (0.425 mol) of diethyl benzylmalonate were added dropwise to a stirred suspension of 28 g (0.7 mol) of NaH (60% dispersion in mineral oil) in 550 mL of absolute ethanol at room temperature. The reaction mixture was refluxed 2 h, then cooled to 50° C. and 47.1 mL (0.425 mol) of ethyl bromoacetate were added dropwise. The reaction mixture was refluxed 2 h, then quenched with 150 mL of water; a solution of 140 g (3.5 mol) of NaOH in 400 mL of water was added and the mixture was heated to reflux for 1 h. EtOH was removed in vacuo, the aqueous solution was washed with Et2O and then carefully brought to acidic pH with 350 mL of 37% HCl and extracted with AcOEt. The solvent was removed in vacuo and the resulting residue was heated to 180° C. for 30 min. After cooling to room temperature, 100 mL of 95% H2SO4 were added and the reaction mixture stirred for 2 h, then it was poured onto 500 g of crushed ice and extracted with Et2O. The organic phase was dried and the solvent removed in vacuo. The resulting residue was taken up in Et2O, washed with 40% NaOH solution then brought to acidic pH with 37% HCl and extracted with Et2O. The organic phase was dried and the solvent removed in vacuo. The resulting solid residue was triturated with Et2O, filtered and dried yielding 15 g of the title compound, used without further purification. m.p.=146-147° C. IR (cm−1): 2924, 1692, 1600; NMR (300 MHz, DMSO, δ ppm): 12.6-12.5 (bs, 1H); 7.9 (d, 1H); 7.6-7.5 (m, 1H); 7.4-7.3 (m, 2H); 3.3-3.1 (m, 3H); 2.7 (m, 2H). MS (m/z): 191.1 (MH+).

1. temperatureThe reaction mixture was refluxed 2 h
2. temperatureThe reaction mixture was refluxed 2 h
3. customquenched with 150 mL of water
4. temperaturethe mixture was heated
5. temperatureto reflux for 1 h
6. customEtOH was removed in vacuo
7. washthe aqueous solution was washed with Et2O
8. extractionextracted with AcOEt
9. customThe solvent was removed in vacuo
10. temperaturethe resulting residue was heated to 180° C. for 30 min
11. temperatureAfter cooling to room temperature
12. addition100 mL of 95% H2SO4 were added
13. additionit was poured onto 500 g of crushed ice
14. extractionextracted with Et2O
15. customThe organic phase was dried
16. customthe solvent removed in vacuo
17. washwashed with 40% NaOH solution
18. extractionextracted with Et2O
19. customThe organic phase was dried
20. customthe solvent removed in vacuo
21. customThe resulting solid residue was triturated with Et2O
22. filtrationfiltered
23. customdried

ORD record

ord-5a9d1ac2aa3a427584bb713697fab47b

Source dataset

uspto-grants-2005_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06969724B2