Diisopropylamine → 3-Ethoxy-4-ethoxycarbonylphenylacetic acid

Temperature

-30 °C

Under an atmosphere of nitrogen, n-butyllithium (25 ml, 15% w/w solution in hexane) was added to a solution of diisopropylamine (3.6 g) in tetrahydrofuran (30 ml) at −30° C. The mixture was stirred at −30° C. for 30 minutes, cooled to −75° C., and hexamethylphosphoramide (HMPA, 10 g) was added slowly. A solution of ethyl 2-ethoxy-4-methylbenzoate (5 g) in tetrahydrofuran (10 ml) was then added at −75° C. and the mixture was stirred for two hours. Carbon dioxide gas was then purged into the reaction mixture at −75° C. till complete decolorization. The reaction mixture was then stirred at −75 to −70° C. for 30 minutes and then brought to 10° C., diluted with water (50 ml), and extracted with ether. The aqueous layer was acidified with 10% aqueous sulphuric acid to pH ˜2 and extracted with dichloromethane. The combined dichloromethane layer was washed with water and concentrated in vacuo. The oily product so obtained was re-dissolved in ether (50 ml) and washed with water. The ethereal layer was then concentrated in vacuo to afford a thick oil which solidified on keeping at room temperature to afford 3-ethoxy-4-(ethoxycarbonyl)phenyl acetic acid 4.4 g (72.7%).

1. temperaturecooled to −75° C.
2. stirringthe mixture was stirred for two hours
3. customCarbon dioxide gas was then purged into the reaction mixture at −75° C. till complete decolorization
4. stirringThe reaction mixture was then stirred at −75 to −70° C. for 30 minutes
5. custombrought to 10° C.
6. additiondiluted with water (50 ml)
7. extractionextracted with ether
8. extractionextracted with dichloromethane
9. washThe combined dichloromethane layer was washed with water
10. concentrationconcentrated in vacuo
11. customThe oily product so obtained
12. washwashed with water
13. concentrationThe ethereal layer was then concentrated in vacuo
14. customto afford a thick oil which
15. customon keeping at room temperature

ORD record

ord-bf07fa0f570b4aebb898b1dbecd1f3c6

Source dataset

uspto-grants-2004_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06686497B1