Hydrochloric Acid → HCID 22221141, compound

To a solution of diethyl malonate (3.38 g) in tetrahydrofuran (40 ml) was gradually added sodium hydride (60%, oil, 770 mg) at 0° C. The mixture was stirred for 10 min and a solution of 4-chloromethyl-5-(2,4-difluorophenyl)isoxazole (2.20 g) in tetrahydrofuran (40 ml) was added dropwise at 0° C. The mixture was stirred at room temperature for 15 hr. The reaction mixture was acidified by pouring into 2N hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layer was concentrated, and the residue was dissolved in a mixture of 6N hydrochloric acid (40 ml) and acetic acid (60 ml) and heated under reflux for 8 hr. The reaction mixture was concentrated, and water was added to the residue. The obtained colorless crystals were filtrated, dried and recrystallized from ethyl acetate-hexane to give a colorless prism (2.10 g, yield 87%) of 3-[5-(2,4-difluorophenyl)-4-isoxazolyl]propionic acid. melting point: 125–126° C.

1. customat 0° C
2. stirringThe mixture was stirred at room temperature for 15 hr
3. extractionextracted with ethyl acetate
4. concentrationThe ethyl acetate layer was concentrated
5. dissolutionthe residue was dissolved in a mixture of 6N hydrochloric acid (40 ml) and acetic acid (60 ml)
6. temperatureheated
7. temperatureunder reflux for 8 hr
8. concentrationThe reaction mixture was concentrated
9. additionwater was added to the residue
10. filtrationThe obtained colorless crystals were filtrated
11. customdried
12. customrecrystallized from ethyl acetate-hexane

ORD record

ord-d16ae31575a344d7870fdd282a2e5389

Source dataset

uspto-grants-2006_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07022725B2