Cyclopropyl methyl ketone → 1080059-85-3

Temperature

120 °C

A mixture of 1-cyclopropylethanone (60 g) and N,N,N′,N′,N″,N″-hexamethylmethanetriamine (103 g) was stirred at 120° C. for 20 hr. The reaction mixture was cooled to room temperature, and concentrated under reduced pressure. To an aqueous solution (200 mL) of the residue was added hydroxyammonium chloride (75 g), and the mixture was heated under reflux for 2 hr. The reaction mixture was extracted with diethyl ether, and the extract was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was applied to silica gel column chromatography (diethyl ether), and the obtained crude product was dissolve in trifluoroacetic anhydride (310 ml). Ammonium nitrate (51.3 g) was gradually added, and the reaction mixture as stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogen carbonate solution was added to the residue, and the mixture was extracted with diethyl ether. The extract was washed successively with saturated sodium hydrogen carbonate, water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was applied to silica gel column chromatography (ethyl acetate), and the obtained crude product was suspended in water (1300 mL). Ammonium chloride (624 g) and zinc powder (250 g) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by NH-silica gel column chromatography (ethyl acetate:hexane=10:90-60:40, volume ratio). The purified product was treated with a 4N hydrochloric acid ethyl acetate solution to give the title compound (23.8 g, yield of 5 steps 25%) as pale-pink crystals.

1. temperatureThe reaction mixture was cooled to room temperature
2. concentrationconcentrated under reduced pressure
3. additionTo an aqueous solution (200 mL) of the residue was added hydroxyammonium chloride (75 g)
4. temperaturethe mixture was heated
5. temperatureunder reflux for 2 hr
6. extractionThe reaction mixture was extracted with diethyl ether
7. washthe extract was washed successively with water and saturated brine
8. dry with materialdried over anhydrous sodium sulfate
9. concentrationconcentrated under reduced pressure
10. customthe obtained crude product
11. stirringthe reaction mixture as stirred at room temperature for 1 hr
12. concentrationThe reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogen carbonate solution
13. additionwas added to the residue
14. extractionthe mixture was extracted with diethyl ether
15. washThe extract was washed successively with saturated sodium hydrogen carbonate, water and saturated brine
16. dry with materialdried over anhydrous magnesium sulfate
17. concentrationconcentrated under reduced pressure
18. customthe obtained crude product
19. stirringthe mixture was stirred at room temperature for 2 hr
20. extractionThe reaction mixture was extracted with ethyl acetate
21. washThe extract was washed successively with water and saturated brine
22. dry with materialdried over anhydrous sodium sulfate
23. concentrationconcentrated under reduced pressure
24. customThe residue was purified by NH-silica gel column chromatography (ethyl acetate:hexane=10:90-60:40, volume ratio)
25. additionThe purified product was treated with a 4N hydrochloric acid ethyl acetate solution

ORD record

ord-bb7f245a48824e94b25fa5690741eec9

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08318746B2