Dimethyl malonate → HCID 18370379, compound

Temperature

0 °C

A 28 % solution of sodium methylate in methanol (19.3 g) and methanol (50 g) are charged in a flask, and the mixture is cooled to 0° C. To the mixture is added dimethyl malonate (13.2 g) and the mixture is stirred at 50° C. for 1 hour. To the mixture is added 1-bromo-5-chloropentane (18.6 g) and stirred under refluxing for 14 hours. The reaction mixture is concentrated under reduced pressure, and to the residue are added toluene (200 g) and water (100 ml) and the mixture is further stirred. The organic layer is separated and magnesium sulfate (10 g) is added to the organic layer. The mixture is filtered and the filtrate is concentrated. Separately, a 43.5 % nitrosylsulfuric acid solution (35.3 g) is charged in another flask and cooled to 0° C. To the mixture is added dropwise the above concentrated organic layer over a period of 1 hour. The mixture is stirred at 0° C. for 1 hour, and the temperature thereof is raised to 20° C. The mixture is stirred at the same temperature for 1 hour. Separately, toluene (100 g) and 10 % aqueous formalin solution (100 g) are charged in another flask and cooled to 5° C. Thereto is added dropwise the above reaction mixture over a period of 1 hour. The reaction mixture is kept at 5° C. for 1 hour, and stirred at 20° C. for 12 hours. The organic layer is separated and washed with water, and to the mixture is added magnesium sulfate (5 g) and filtered. The filtrate is concentrated under reduced pressure to give crude methyl 7-chloro-2-oxoheptanoate (24 g), which is purified by distillation under reduced pressure to give methyl 7-chloro-2-oxoheptanoate (14.3 g).

1. stirringstirred
2. temperatureunder refluxing for 14 hours
3. concentrationThe reaction mixture is concentrated under reduced pressure
4. additionto the residue are added toluene (200 g) and water (100 ml)
5. customThe organic layer is separated
6. additionmagnesium sulfate (10 g) is added to the organic layer
7. filtrationThe mixture is filtered
8. concentrationthe filtrate is concentrated
9. additionSeparately, a 43.5 % nitrosylsulfuric acid solution (35.3 g) is charged in another flask
10. temperaturecooled to 0° C
11. additionTo the mixture is added dropwise the above concentrated organic layer over a period of 1 hour
12. stirringThe mixture is stirred at 0° C. for 1 hour
13. temperaturethe temperature thereof is raised to 20° C
14. stirringThe mixture is stirred at the same temperature for 1 hour
15. additionSeparately, toluene (100 g) and 10 % aqueous formalin solution (100 g) are charged in another flask
16. temperaturecooled to 5° C
17. additionThereto is added dropwise the above reaction mixture over a period of 1 hour
18. waitThe reaction mixture is kept at 5° C. for 1 hour
19. stirringstirred at 20° C. for 12 hours
20. customThe organic layer is separated
21. washwashed with water
22. additionto the mixture is added magnesium sulfate (5 g)
23. filtrationfiltered
24. concentrationThe filtrate is concentrated under reduced pressure
25. customto give crude methyl 7-chloro-2-oxoheptanoate (24 g), which
26. distillationis purified by distillation under reduced pressure

ORD record

ord-64cda1eba5024338880fc1e9492ee7c7

Source dataset

uspto-grants-1993_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05268501