Ethyl 2-bromopropionate → HCID 12769847, compound

To a mixture of 1.2 g (0.05 mole) of magnesium turnings and 50 ml of anhydrous tetrahydrofuran was added under a nitrogen stream one drop of ethyl bromide, followed by adding 10 g (0.0395 mole) of 4-(3-methyl-2-thienyl)-1-bromobenzene (boiling point 171°-175° C./16-17 mmHg). After refluxing for 30 minutes, the mixture was cooled. To the mixture was added a solution of 2.8 g (0.0205 mole) of anhydrous zinc chloride in 50 ml of anhydrous tetrahydrofuran, and the mixture was stirred at room temperature for 3 hours. To the mixture was added 7.2 g (0.0398 mole) of ethyl 2-bromopropionate. After having been stirred at 50° to 60° C. for one hour, the mixture was freed from the solvent by distillation under reduced pressure. The residue was mixed with 50 ml of 2 N hydrochloric acid and 50 ml of benzene. The organic layer was separated, washed with water, and freed from the solvent by distillation under reduced pressure. The residue was mixed with 50 ml of an ethanol solution containing 2.3 g of sodium hydroxide, heated under reflux for 3 hours, and then freed from the ethanol by distillation. The residue was mixed with 100 ml of water and 50 ml of benzene. The aqueous layer was separated, neutralized with hydrochloric acid, and the liberated oily substance was extracted with cyclohexane. The extract solution was dried over anhydrous magnesium sulfate and freed from the solvent by distillation under reduced pressure. The residue was purified by silica gel column chromatography (developing solvent: cyclohexane) to obtain 3.2 g (32.9% yield) of intended 2-[4-(3-methyl-2-thienyl)phenyl]propionic acid.

1. additionwas added under a nitrogen
2. temperatureAfter refluxing for 30 minutes
3. temperaturethe mixture was cooled
4. stirringAfter having been stirred at 50° to 60° C. for one hour
5. distillationthe mixture was freed from the solvent by distillation under reduced pressure
6. additionThe residue was mixed with 50 ml of 2 N hydrochloric acid and 50 ml of benzene
7. customThe organic layer was separated
8. washwashed with water
9. distillationfreed from the solvent by distillation under reduced pressure
10. additionThe residue was mixed with 50 ml of an ethanol solution
11. additioncontaining 2.3 g of sodium hydroxide
12. temperatureheated
13. temperatureunder reflux for 3 hours
14. distillationfreed from the ethanol by distillation
15. additionThe residue was mixed with 100 ml of water and 50 ml of benzene
16. customThe aqueous layer was separated
17. extractionthe liberated oily substance was extracted with cyclohexane
18. dry with materialThe extract solution was dried over anhydrous magnesium sulfate
19. distillationfreed from the solvent by distillation under reduced pressure
20. customThe residue was purified by silica gel column chromatography (developing solvent: cyclohexane)

ORD record

ord-8cc6305b60624e059e2bd32e305780d7

Source dataset

uspto-grants-1980_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04230719