Diethyl Malonate → Ethyl 3-oxo-3-(2,4,5-trifluoro-3-methylphenyl)propanoate

温度

80 °C

2.4 g of magnesium, 10 ml of ethanol, and 0.4 ml of carbon tetrachloride were stirred in a three necked flask at room temperature for activation, and 15 ml of diethyl malonate and 40 ml of tetrahydrofuran were gradually added dropwise. The mixture was stirred at 80° C. for 4 hours. The reaction solution was allowed to cool, and then cooled to −40° C. To 50 ml solution in methylene chloride of 15.5 g of 2,4,5-trifluoro-3-methylbenzoic acid obtained in Reference Example 1(3) were added 8 ml of oxalyl dichloride and 5 drops of N,N-dimethylformamide, and the mixture was stirred at room temperature for 3 hours. The solvent was distilled off, and tetrahydrofuran was added for azeotropic distillation. The residue was dissolved in 40 ml of tetrahydrofuran, and this solution was gradually added dropwise to the above-described reaction solution at −40° C. After the dropwise addition, the reaction solution was stirred at room temperature for 3 days, and the solvent was distilled off. 50 ml of 12N hydrochloric acid was added to the solution to about pH 2, and the solution was extracted with chloroform, and solvent was distilled off. To the residue were added 30 ml of water and 0.6 g of p-toluenesulfonic acid, and the mixture was stirred under reflux for 6 hours. The reaction solution was allowed to cool, extracted with chloroform, and washed with water and 5% aqueous solution of sodium hydrogencarbonate successively. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure to obtain the title compound as 5.5 g of powder and 10.2 g of brown oil.

1. additionwere gradually added dropwise
2. temperatureto cool
3. temperaturecooled to −40° C
4. stirringthe mixture was stirred at room temperature for 3 hours
5. distillationThe solvent was distilled off
6. additiontetrahydrofuran was added for azeotropic distillation
7. dissolutionThe residue was dissolved in 40 ml of tetrahydrofuran
8. additionthis solution was gradually added dropwise to the above-described reaction solution at −40° C
9. additionAfter the dropwise addition
10. stirringthe reaction solution was stirred at room temperature for 3 days
11. distillationthe solvent was distilled off
12. addition50 ml of 12N hydrochloric acid was added to the solution to about pH 2
13. extractionthe solution was extracted with chloroform, and solvent
14. distillationwas distilled off
15. additionTo the residue were added 30 ml of water and 0.6 g of p-toluenesulfonic acid
16. stirringthe mixture was stirred
17. temperatureunder reflux for 6 hours
18. temperatureto cool
19. extractionextracted with chloroform
20. washwashed with water and 5% aqueous solution of sodium hydrogencarbonate successively
21. dry with materialThe organic layer was dried over magnesium sulfate
22. concentrationconcentrated under reduced pressure

ORDレコード

ord-a366275bed5f42cd833f2c414df829d2

出典データセット

uspto-grants-2001_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06211375B1