Triethylamine → 4-cyclopropyl-5-methyl-1H-imidazole

Temperature

60 °C

4-Cyclopropyl-5-methyl-1H-imidazole was synthesized according to the following procedure: Under nitrogen with stirring formamidine acetate (15.62 g, 150 mmol) was suspended in 40 ml anhydrous ethanol. 2-bromo-1-cyclopropylpropan-1-one (2.64 g, 15 mmol) was added via syringe and the mixture was heated to 60° C. for 2 hours. Triethylamine (21 ml, 155 mmol) was then added and the reaction was heated for an additional 12 hours at 60° C. The solvent was removed under reduced pressure, and the residue was dissolved in 50 ml of water. An aqueous solution of saturated sodium bicarbonate (20 ml) was added, followed by sodium chloride until the solution became saturated. The mixture was placed in a separatory funnel and extracted with ethyl acetate (3×50 ml), the organic extracts combined, dried over magnesium sulfate, filtered and then the solvent removed under reduced pressure. The oily residue was washed with hexanes (2×100 ml) to remove any residual triethylamine, leaving an oily residue which was >90% pure by 1H-NMR, which was further purified by loading onto a silica gel column in ethyl acetate and eluting with 0 to 10% methanol in ethyl acetate. Yield 0.607 g, 33%

1. temperaturethe reaction was heated for an additional 12 hours at 60° C
2. customThe solvent was removed under reduced pressure
3. dissolutionthe residue was dissolved in 50 ml of water
4. additionAn aqueous solution of saturated sodium bicarbonate (20 ml) was added
5. customThe mixture was placed in a separatory funnel
6. extractionextracted with ethyl acetate (3×50 ml)
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. customthe solvent removed under reduced pressure
10. washThe oily residue was washed with hexanes (2×100 ml)
11. customto remove any residual triethylamine
12. customleaving an oily residue which
13. customwas further purified
14. washeluting with 0 to 10% methanol in ethyl acetate

ORD record

ord-b90a3776f6364711946b2f0b322340f3

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08927582B2