Methyl iodide → 1,3-Cyclopentanedione, 2,2-dimethyl-

A mixture of 2-methylcyclopentane-1,3-dione (49.98 g, 446 mmol), potassium hydroxide (25.5 g, 455 mmol) and iodomethane (30.1 mL, 481 mmol) in dioxane (390 mL) and water (130 mL) was heated to reflux for 5 h. A biphasic mixture of potassium hydroxide (10.4 g), iodomethane (12.5 mL), water (26 mL) and dioxane (78 mL) was added. The mixture was heated at reflux for 3 additional hours and then stirred at ambient temperature overnight. Another portion of a biphasic mixture of potassium hydroxide (10.4 g), iodomethane (12.5 mL), water (26 mL) and dioxane (78 mL) was added. The mixture was heated at reflux for 3 h, cooled to room temperature and extracted with ether (600 mL, then 2×400 mL). The combined extracts were concentrated using a rotavap while keeping the bath temperature at or below room temperature to prevent loss of volatile product. The residue was treated with 10% hydrochloric acid (250 mL) and placed in a 120° C. oil bath until it started to boil (˜15 min). The mixture was cooled with an ice-water bath, diluted with water (250 mL) and treated with careful addition of sodium carbonate until carbon dioxide release stopped. The pH of the solution was 8-9. The mixture was extracted with dichloromethane (4×200 mL). The combined extracts were dried (MgSO4), filtered and concentrated while keeping water bath at or below room temperature. The residue was further dried under vacuum briefly to remove residual solvent to give 2,2-dimethylcyclopentane-1,3-dione as tan solid (38.1 g, 68% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 2.81 (4H, s), 1.16 (6H, s); LC retention time: 0.990 min (analytical HPLC Method F).

1. temperaturewas heated
2. temperatureto reflux for 5 h
3. additionwas added
4. temperatureThe mixture was heated
5. temperatureat reflux for 3 additional hours
6. additionwas added
7. temperatureThe mixture was heated
8. temperatureat reflux for 3 h
9. temperaturecooled to room temperature
10. extractionextracted with ether (600 mL
11. concentrationThe combined extracts were concentrated
12. custombelow room temperature
13. additionThe residue was treated with 10% hydrochloric acid (250 mL)
14. customplaced in a 120° C.
15. custom(˜15 min)
16. temperatureThe mixture was cooled with an ice-water bath
17. additiondiluted with water (250 mL)
18. additiontreated with careful addition of sodium carbonate until carbon dioxide release
19. extractionThe mixture was extracted with dichloromethane (4×200 mL)
20. dry with materialThe combined extracts were dried (MgSO4)
21. filtrationfiltered
22. concentrationconcentrated
23. custombelow room temperature
24. customThe residue was further dried under vacuum briefly
25. customto remove residual solvent

ORD record

ord-5836d98f1bd846faa0ac09ab91680fb9

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08921368B2