Trifluoroacetic acid → HCID 59389292, compound

The compound of Example 350 (1.00 g) was dissolved in tetrahydrofuran (43 mL) in an argon atmosphere. While this solution was chilled in an ice bath, lithium bis(trimethylsilyl) amide (4.77 mL, 1.0 mol/L tetrahydrofuran solution) was added and the mixture was stirred for 15 min while ice-chilled. While the mixture was kept ice-chilled, t-butyl bromoacetate (0.954 mL) was added and the mixture was stirred at room temperature for 1 hour. With the mixture being ice-chilled, a saturated aqueous ammonium chloride solution was added and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. Evaporation of the solvent gave a yellow oil. This product was dissolved in dichloromethane (10 mL). While the solution was kept ice-chilled, trifluoroacetic acid (5 mL) was added and the mixture was stirred at room temperature for 19 hours. Subsequently, dichloromethane was evaporated and the residue was diluted with water, followed by addition of a 10% sodium hydroxide solution to make the mixture basic. The mixture was then washed with diethyl ether. Diluted hydrochloric acid was added to the aqueous layer to make it acidic and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated to give a yellow oil. This product was dissolved in ethanol (29 mL). To the solution, hydrazine monohydrate (0.40 mL) was added and the mixture was stirred for 4 hours under reflux. Evaporation of the solvent and subsequent purification of the residue by silica gel chromatography (hexane:ethyl acetate=2:3) afforded the title compound as a colorless amorphous material (1.00 g).

1. temperatureWhile this solution was chilled in an ice bath
2. temperaturechilled
3. temperaturechilled
4. stirringthe mixture was stirred at room temperature for 1 hour
5. temperaturechilled
6. extractionthe mixture was extracted with ethyl acetate
7. washThe extract was washed with saturated brine
8. dry with materialdried over anhydrous sodium sulfate
9. customEvaporation of the solvent
10. customgave a yellow oil
11. temperaturechilled
12. stirringthe mixture was stirred at room temperature for 19 hours
13. customSubsequently, dichloromethane was evaporated
14. additionthe residue was diluted with water
15. additionfollowed by addition of a 10% sodium hydroxide solution
16. washThe mixture was then washed with diethyl ether
17. additionDiluted hydrochloric acid was added to the aqueous layer
18. extractionthe mixture was extracted with ethyl acetate
19. dry with materialThe organic layer was dried over anhydrous sodium sulfate
20. customthe solvent was evaporated
21. customto give a yellow oil
22. stirringthe mixture was stirred for 4 hours
23. temperatureunder reflux
24. customEvaporation of the solvent and subsequent purification of the residue by silica gel chromatography (hexane:ethyl acetate=2:3)

ORD record

ord-4a09aad8b497432bbf55c2ad69e3ab95

Source dataset

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07763617B2