Phenol → HCID 67198881, compound

Cyclobutylideneethanol (22.14 g, <60 mmol) was dissolved in triethyl orthoacetate (25 mL). To the solution, phenol (1.02 g, 11.6 mmol) was added, and the mixture was stirred for 1 day under heating to reflux. The mixture was allowed to cool, and saturated saline was then added thereto, followed by extraction with ethyl acetate. The organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. To the residue, a 2 N potassium hydroxide-methanol solution (80 mL) was added, and the mixture was stirred overnight at room temperature. The solvent was distilled off under reduced pressure, and the residue was then dissolved in a 2 N aqueous sodium hydroxide solution and washed with diethyl ether. The aqueous layer was made acidic using concentrated hydrochloric acid under ice cooling, followed by extraction with ethyl acetate. The organic layer was washed with saturated saline and then dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was dissolved in tetrahydrofuran (70 mL). To the solution, lithium aluminum hydride (948.8 mg, 25 mmol) was then added under ice cooling. The mixture was brought to room temperature and then stirred for 7 hours under heating to reflux. Methanol (1.5 mL) and a 1 N aqueous sodium hydroxide solution (1.5 mL) were added thereto under ice cooling, and the mixture was further stirred at room temperature for 1 hour and then filtered through Celite. The residue was washed with dichloromethane and saturated saline. These filtrates were combined and separated into aqueous and organic layers. The organic layer was washed with a 1 N aqueous sodium hydroxide solution and saturated saline and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain the compound of interest as a colorless oil substance (1.94 g, 25%).

1. temperatureunder heating to reflux
2. temperatureto cool
3. additionsaturated saline was then added
4. extractionfollowed by extraction with ethyl acetate
5. washThe organic layer was washed with saturated saline
6. dry with materialdried over anhydrous sodium sulfate
7. distillationthe solvent was distilled off under reduced pressure
8. additionTo the residue, a 2 N potassium hydroxide-methanol solution (80 mL) was added
9. stirringthe mixture was stirred overnight at room temperature
10. distillationThe solvent was distilled off under reduced pressure
11. dissolutionthe residue was then dissolved in a 2 N aqueous sodium hydroxide solution
12. washwashed with diethyl ether
13. extractionfollowed by extraction with ethyl acetate
14. washThe organic layer was washed with saturated saline
15. dry with materialdried over anhydrous magnesium sulfate
16. distillationthe solvent was distilled off under reduced pressure
17. dissolutionThe residue was dissolved in tetrahydrofuran (70 mL)
18. customwas brought to room temperature
19. stirringstirred for 7 hours
20. temperatureunder heating to reflux
21. stirringunder ice cooling, and the mixture was further stirred at room temperature for 1 hour
22. filtrationfiltered through Celite
23. washThe residue was washed with dichloromethane and saturated saline
24. customseparated into aqueous and organic layers
25. washThe organic layer was washed with a 1 N aqueous sodium hydroxide solution and saturated saline
26. dry with materialdried over anhydrous sodium sulfate
27. distillationThe solvent was distilled off under reduced pressure
28. customto obtain the compound of interest as a colorless oil substance (1.94 g, 25%)

ORD record

ord-83b4f0b0122541558a588fdfc6b8c660

Source dataset

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07947738B2