Hexane → HCID 86697462, compound

To 1-(2,2-dimethyl-1,1-diphenylpropyl)-2-(propan-2-ylidene)hydrazine (147 mg, 0.500 mmol) in tetrahydrofuran (5 mL), 1.61 M n-butylithium in hexane (0.37 mL, 0.60 mmol) was added dropwise at −78° C., and after 1 hour of stirring at the same temperature, p-bromobenzyl bromide (125 mg, 0.50 mmol) was added dropwise. The reaction solution was stirred at the same temperature for 1 hour, warmed to room temperature and stirred at room temperature for 18 hours. The reaction solution was quenched with saturated aqueous sodium hydrogen carbonate and extracted with ethyl acetate (10 mL×3). The resulting organic layer was concentrated under reduced pressure, and the resulting residue was dissolved in 2 mL of ethanol, mixed with trifluoroacetic acid (1 mL) and stirred at room temperature for 24 hours. After the stirring, the reaction solution was mixed with concentrated hydrochloric acid (3 mL) and stirred at 80° C. for 5 hours. After the stirring, the reaction solution was neutralized with saturated aqueous sodium hydrogen carbonate and extracted with methylene chloride. The resulting organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in toluene (3.0 mL) and acetic acid (70 μL), mixed with methyl isobutyrylacetic acid (72 mg, 0.50 mmol) and stirred at 90° C. for 3 hours. The reaction solution was allowed to cool to room temperature, diluted with ethyl acetate and washed with saturated aqueous sodium hydrogen carbonate and then with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by intermediate pressure silica gel column chromatography (silica gel12 g, ethyl acetate:hexane=1:9 to 3:7) to give 15 mg of the desired product as a brown oil.

1. additionwas added dropwise
2. stirringstirred at room temperature for 18 hours
3. customThe reaction solution was quenched with saturated aqueous sodium hydrogen carbonate
4. extractionextracted with ethyl acetate (10 mL×3)
5. concentrationThe resulting organic layer was concentrated under reduced pressure
6. dissolutionthe resulting residue was dissolved in 2 mL of ethanol
7. additionmixed with trifluoroacetic acid (1 mL)
8. stirringstirred at room temperature for 24 hours
9. additionAfter the stirring, the reaction solution was mixed with concentrated hydrochloric acid (3 mL)
10. stirringstirred at 80° C. for 5 hours
11. extractionextracted with methylene chloride
12. washThe resulting organic layer was washed with saturated aqueous sodium chloride
13. dry with materialdried over anhydrous sodium sulfate
14. filtrationfiltered
15. concentrationthe filtrate was concentrated under reduced pressure
16. dissolutionThe resulting residue was dissolved in toluene (3.0 mL)
17. stirringstirred at 90° C. for 3 hours
18. temperatureto cool to room temperature
19. washwashed with saturated aqueous sodium hydrogen carbonate
20. dry with materialwith saturated aqueous sodium chloride, dried over anhydrous sodium sulfate
21. filtrationfiltered
22. concentrationthe filtrate was concentrated under reduced pressure
23. customThe resulting residue was purified by intermediate pressure silica gel column chromatography (silica gel12 g, ethyl acetate:hexane=1:9 to 3:7)

ORD record

ord-10df54bc1cac4630a0568cc3dc13583d

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658686B2