Acetic Acid → (2E)-3-[5-(4-fluorophenyl)-1,2,3-thiadiazol-4-yl]acrylic acid

[5-(4-Fluorophenyl)-1,2,3-thiadiazol-4-yl]methanol (0.75 g) was dissolved in tetrahydrofuran (30 ml) and activated manganese dioxide (3 g) was added. The mixture was stirred at room temperature for 16 hrs. The reaction mixture was filtered and the filtrate was concentrated. Ethyl diethylphosphonoacetate (0.50 g) and N,N-dimethylformamide (10 ml) were added to the residue. To this mixture was added sodium hydride (60% in oil, 80 mg) at 0° C. and the mixture was stirred at 0° C. for 1 hr. The reaction mixture was poured into an aqueous dilute hydrochloric acid solution and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated to give a yellow oil. A 6N aqueous hydrochloric acid solution (10 ml) and acetic acid (5 ml) were added to this yellow oil and the mixture was stirred for 3 hrs. with heating under reflux. The reaction mixture was concentrated, poured into water, and the precipitated solids were filtered, washed with water and dried to give (2E)-3-[5-(4-fluorophenyl)-1,2,3-thiadiazol-4-yl]acrylic acid (190 mg, yield: 21%) as pale-yellow crystals.

1. filtrationThe reaction mixture was filtered
2. concentrationthe filtrate was concentrated
3. additionEthyl diethylphosphonoacetate (0.50 g) and N,N-dimethylformamide (10 ml) were added to the residue
4. additionTo this mixture was added sodium hydride (60% in oil, 80 mg) at 0° C.
5. stirringthe mixture was stirred at 0° C. for 1 hr
6. additionThe reaction mixture was poured into an aqueous dilute hydrochloric acid solution
7. extractionextracted with ethyl acetate
8. washThe organic layer was washed with saturated brine
9. dry with materialdried over anhydrous magnesium sulfate
10. concentrationconcentrated
11. customto give a yellow oil
12. stirringthe mixture was stirred for 3 hrs
13. temperaturewith heating
14. temperatureunder reflux
15. concentrationThe reaction mixture was concentrated
16. additionpoured into water
17. filtrationthe precipitated solids were filtered
18. washwashed with water
19. customdried

ORD record

ord-e77d16bdc41449129e8f0ef99e4009a6

Source dataset

uspto-grants-2008_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07423159B2