Methane → 3-(4-Bromophenyl)-2-methylpropanoic acid

Temperature

205 °C

A solution of sodium hydroxide (34.0 g) in water (155 ml) was added to a solution of diethyl 2-(4-bromobenzyl)-2-methylmalonate (29.2 g) in ethanol (165 ml), and then heated under reflux for 9 hours. The reaction mixture was cooled, the solvent was evaporated and the residue taken up in water (150 ml). Sodium hydroxide pellets were added (25.4 g) and the reaction mixture was heated under reflux for 2 hours. The reaction mixture was then cooled and acidified to pH<1 with concentrated hydrochloric acid, which caused precipitation of a solid. The reaction mixture was extracted with diethyl ether (3×150 ml), the combined organic layers were dried (MgSO4) and then the solvent was evaporated to give a white solid. This solid was heated at 205° C. for 20 minutes, cooled to ambient temperature, dissolved in 1.0 M sodium hydroxide solution (150 ml), treated with activated charcoal and then filtered through diatomaceous earth. The resulting clear solution was re-acidified and then extracted with diethyl ether (3×150 ml). The combined organic layers were dried (MgSO4) and evaporated to give a yellow oil which crystallised on standing to give 2-methyl-3-(4-bromophenyl)propanoic acid as a white solid (18.2 g), m.p. 69-70° C.; mass spectrum (+ve CI): 243 (M+H)+.

1. temperatureheated
2. temperatureunder reflux for 9 hours
3. temperatureThe reaction mixture was cooled
4. customthe solvent was evaporated
5. additionSodium hydroxide pellets were added (25.4 g)
6. temperaturethe reaction mixture was heated
7. temperatureunder reflux for 2 hours
8. temperatureThe reaction mixture was then cooled
9. customprecipitation of a solid
10. extractionThe reaction mixture was extracted with diethyl ether (3×150 ml)
11. dry with materialthe combined organic layers were dried (MgSO4)
12. customthe solvent was evaporated
13. customto give a white solid
14. temperaturecooled to ambient temperature
15. filtrationfiltered through diatomaceous earth
16. extractionextracted with diethyl ether (3×150 ml)
17. dry with materialThe combined organic layers were dried (MgSO4)
18. customevaporated
19. customto give a yellow oil which
20. customcrystallised

ORD record

ord-4d64422910c94be7949957d287e137f4

Source dataset

uspto-grants-2000_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06060475