Hydrochloric Acid → HCID 85940291, compound

Temperature

-78 °C

Lithium aluminum hydride (0.74 g, 20 mmol) was added to a tetrahydrofuran solution (30 mL) of ethyl 2-allylpent-4-ene-acetate (2.20 g, 13.1 mmol) under ice cooling, and the mixture was stirred in this state for 1 hour. To the reaction solution, a 1 N aqueous sodium hydroxide solution (10 mL) was added, and the mixture was stirred at room temperature for 1 hour and then filtered through Celite. The filtrate was diluted with saturated saline and ethyl acetate and separated into aqueous and organic layers. The organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. A dichloromethane solution (20 mL) of oxalyl chloride (1.6 mL, 13.1 mmol) was added dropwise to a dichloromethane solution (10 mL) of dimethyl sulfoxide (2.7 mL, 19.5 mmol) under cooling to −78° C. To the reaction solution, a dichloromethane (10 mL) solution of the above-obtained residue was added, and this mixture was stirred at −78° C. for 1 hour. To the reaction solution, triethylamine (7.1 mL, 52.4 mmol) was added, and the mixture was stirred at room temperature for 1 hour. 1 N hydrochloric acid and saturated saline were added thereto, 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 obtained residue was dissolved in pyridine (2.3 mL). To the solution, malonic acid (1.55 g, 14.95 mmol) and pyrrolidine (0.43 mL) were added, and the mixture was stirred overnight at room temperature and further stirred for 6 hours under heating to reflux. The mixture was allowed to cool, then diluted with a 2 N aqueous sodium hydroxide solution, and then washed with dimethyl ether. The aqueous layer was made acidic using concentrated hydrochloric acid under ice cooling, followed by extraction with diethyl ether. The organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain the compound of interest as a pale yellow oil substance (1.49 g, 78%).

1. stirringthe mixture was stirred at room temperature for 1 hour
2. filtrationfiltered through Celite
3. additionThe filtrate was diluted with saturated saline and ethyl acetate
4. customseparated into aqueous and organic layers
5. washThe organic layer was washed with saturated saline
6. dry with materialdried over anhydrous magnesium sulfate
7. distillationthe solvent was distilled off under reduced pressure
8. stirringthis mixture was stirred at −78° C. for 1 hour
9. stirringthe mixture was stirred at room temperature for 1 hour
10. extractionfollowed by extraction with ethyl acetate
11. washThe organic layer was washed with saturated saline
12. dry with materialdried over anhydrous magnesium sulfate
13. distillationthe solvent was distilled off under reduced pressure
14. dissolutionThe obtained residue was dissolved in pyridine (2.3 mL)
15. stirringthe mixture was stirred overnight at room temperature
16. stirringfurther stirred for 6 hours
17. temperatureunder heating to reflux
18. temperatureto cool
19. washwashed with dimethyl ether
20. extractionfollowed by extraction with diethyl ether
21. washThe organic layer was washed with saturated saline
22. dry with materialdried over anhydrous magnesium sulfate
23. distillationThe solvent was distilled off under reduced pressure
24. customto obtain the compound of interest as a pale yellow oil substance (1.49 g, 78%)

ORD record

ord-104ecbc6a58940abbcb041daa43996e1

Source dataset

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07947738B2