Diethyl Malonate → 3-(3,4-dimethylphenyl)propanoic Acid

Temperature

0 °C

To a solution of 70.0 ml of diethyl malonate dissolved in 400 ml of dry ethanol was added 10.0 g of metalic sodium. The reaction mixture was stirred for 30 minutes and cooled to 0° C; and 66.5 g of 3,4-dimethylbenzyl chloride was added thereto. This reaction mixture was stirred for 1 hour at room temperature, heated at the boiling temperature for 4 hours and concentrated under reduced pressure to produce residues, which were dissolved in ethyl ether. This ethereal solution was washed with water. To the residues obtained after a further concentration of the organic phase were added 500 ml of water and 170 g of KOH; and this mixture was heated at the boiling temperature for 24 hours. This mixture was concentrated under reduced pressure until about a half of the amount remained, and 200 ml of sulfuric acid was then slowly added thereto. The resultant solution was heated at the boiling temperature for 24 hours, extracted twice with 300 ml of ethyl ether and evaporated under reduced pressure to obtain solids, which were recrystallized from boiling hexane to provide 42.1 g of 3-(3,4-dimethylphenyl)propanoic acid as a white solid (yield 55%), having the characteristics of: m.p. 82° C.; NMR(CDCl3, 300 MHz) δ2.22(s, 3H, CH3), 2.24(s, 3H, CH3), 2.66(t, J=8 Hz, 2H, ArCH2), 2.89(t, J=8 Hz, 2H, CH2CO), 6.93~7.70(m, 3H, ArH).

1. stirringThis reaction mixture was stirred for 1 hour at room temperature
2. temperatureheated at the boiling temperature for 4 hours
3. concentrationconcentrated under reduced pressure
4. customto produce residues, which
5. washThis ethereal solution was washed with water
6. customTo the residues obtained
7. concentrationafter a further concentration of the organic phase
8. additionwere added 500 ml of water and 170 g of KOH
9. temperatureand this mixture was heated at the boiling temperature for 24 hours
10. concentrationThis mixture was concentrated under reduced pressure until about a half of the amount
11. addition200 ml of sulfuric acid was then slowly added
12. temperatureThe resultant solution was heated at the boiling temperature for 24 hours
13. extractionextracted twice with 300 ml of ethyl ether
14. customevaporated under reduced pressure
15. customto obtain solids, which
16. customwere recrystallized

ORD record

ord-a6a4e383f46e49689e82ca555e0f2d07

Source dataset

uspto-grants-1993_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05242944