Hydrochloric Acid → Methyl (1-vinylcyclobutyl)acetate

Temperature

-78 °C

To an ice-cooled solution of diisopropylamine (1.07 mL) in THF (10 mL) was added 1.57 M n-butyllithium/hexane (4.47 mL) dropwise over 5 minutes. After stirring under ice cooling for additional 30 minutes, the reaction solution was cooled to −78° C. and a solution of 2-cyclobutyridene ethyl acetate (0.89 g) in tetrahydrofuran (0.8 mL) was added thereto dropwise over 5 minutes. After stirring the reaction solution at that temperature for 1 hour, chlorotrimethylsilane (0.97 mL) was added dropwise over 5 minutes. The reaction solution was stirred at room temperature for 1 hour, and then, heated under reflux for 4.5 hours. The reaction solution was ice-cooled, to which methanol (2 mL) and a 3N aqueous sodium hydroxide solution (5 ml) were added. The solution was stirred for 30 minutes. Then, conc. hydrochloric acid (2 mL) was added to the solution and it was stirred for additional 30 minutes. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue (1.77 g) was dissolved in N,N-dimethylformamide (10 mL), to which potassium carbonate (2.82 g) and methyl iodide (0.62 mL) were added. The solution was stirred at room temperature for 1 hour. The reaction solution was filtered with Celite and insolubles on Celite were washed with ethyl acetate. The filtrate was combined with the wash, and it washed in turn with 1N hydrochloric acid and saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by chromatography [silica gel, hexane-ethyl acetate (20:1)] to give the title compound (0.67 g).

1. waitdropwise over 5 minutes
2. stirringAfter stirring the reaction solution at that temperature for 1 hour
3. stirringThe reaction solution was stirred at room temperature for 1 hour
4. temperatureheated
5. temperatureunder reflux for 4.5 hours
6. stirringThe solution was stirred for 30 minutes
7. stirringwas stirred for additional 30 minutes
8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
9. concentrationconcentrated under reduced pressure
10. dissolutionThe resulting residue (1.77 g) was dissolved in N,N-dimethylformamide (10 mL), to which potassium carbonate (2.82 g) and methyl iodide (0.62 mL)
11. additionwere added
12. stirringThe solution was stirred at room temperature for 1 hour
13. filtrationThe reaction solution was filtered with Celite and insolubles on Celite
14. washwere washed with ethyl acetate
15. washwashed in turn with 1N hydrochloric acid and saturated aqueous sodium chloride solution
16. dry with materialThe organic layer was dried over anhydrous sodium sulfate
17. concentrationconcentrated under reduced pressure
18. customThe resulting residue was purified by chromatography [silica gel, hexane-ethyl acetate (20:1)]

ORD record

ord-9ab7d8dcf513466a89ee5fbf9047d4c1

Source dataset

uspto-grants-2008_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07375115B2