Hydrochloric Acid → HCID 178481735, compound

Potassium ethyl malonate (22.1 g (0.13 mol)) was suspended in 200 mL of ethyl acetate, and 29.14 g (0.29 mol) of triethylamine and 13.7 g (0.14 mol) of magnesium chloride were sequentially added thereto with stirring under ice cooling. The resulting suspension liquid was stirred at 40° C. for 6 hours and again ice-cooled, and 20.9 g (0.1 mol) of 2,4-dichlorobenzoyl chloride was added dropwise thereto over 1 hour while keeping the reaction solution at 10° C. or less. After the dropwise addition, the stirring was continued at room temperature for 12 hours. Subsequently, 200 mL of 5% hydrochloric acid was added dropwise to the reaction solution, and the organic layer was separated. The obtained organic layer was washed twice with 50 mL of water and then with 30 mL of saturated brine, and the solvent was removed by distillation under reduced pressure. To the residue obtained by the concentration, 100 mL of ethanol was added. The resulting solution was cooled to 10° C. or less with stirring, and 13.1 g (0.1 mol) of an aqueous 35% methylhydrazine solution was added dropwise thereto over 1 hour. After the dropwise addition, the solution was stirred at room temperature for 1 hour and then at 80° C. for 3 hours. When the reaction was completed, the reaction solution was cooled to room temperature, 300 mL of water was added, and the produced crystal was collected by filtration. The crystal was washed twice with 50 mL of water and dried by a hot air drier to obtain 12.3 g (yield: 50.2%) of the title compound as a white crystal. 1H-NMR value (300 MHz, CDCl3): σ=7.53 (d; J=1.8 Hz, 1H), 7.2-7.4 (m, 2H), 5.68 (s, 1H), 3.54 (s, 3H) ppm.

1. stirringThe resulting suspension liquid was stirred at 40° C. for 6 hours
2. temperatureagain ice-cooled
3. customat 10° C. or less
4. additionAfter the dropwise addition
5. waitthe stirring was continued at room temperature for 12 hours
6. customthe organic layer was separated
7. washThe obtained organic layer was washed twice with 50 mL of water
8. customwith 30 mL of saturated brine, and the solvent was removed by distillation under reduced pressure
9. customTo the residue obtained by the concentration, 100 mL of ethanol
10. additionwas added
11. temperatureThe resulting solution was cooled to 10° C. or less
12. stirringwith stirring
13. waitover 1 hour
14. additionAfter the dropwise addition
15. stirringthe solution was stirred at room temperature for 1 hour
16. waitat 80° C. for 3 hours
17. filtrationthe produced crystal was collected by filtration
18. washThe crystal was washed twice with 50 mL of water
19. customdried by a hot air drier

ORD record

ord-3be161ed6ed14f50b689c4659ddf5d3d

Source dataset

uspto-grants-2009_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07488831B2