Ammonium Chloride → HCID 67530783, compound

Temperature

23 °C

A stirred solution of 5.0 grams (0.012 mole) of 1-(triphenylmethyl)-4-iodoimidazole (vii) in about 200 mL of anhydrous methylene chloride was cooled to about 21° C., and 3.84 mL (3.0M in diethyl ether: 0.012 mole) of ethylmagnesium bromide was added. Upon completion of addition, the reaction mixture was stirred for about one hour at 23° C., and then a solution of 2.0 grams (0.012 mole) of 6-methoxy-5-methylindan-1-one (ii) (prepared in a manner analogous to Step D of Example 1) in 50 mL of methylene chloride was added in one portion. Upon completion of addition, the reaction mixture was stirred at ambient temperature for about 18 hours. After this time, the reaction mixture was poured into a separatory funnel containing an aqueous saturated solution of ammonium chloride. The organic layer was separated and the aqueous layer was extracted with two portions of methylene chloride. The combined extracts and organic layer were dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue. The residue was dissolved in methanol and aqueous 4N hydrochloric acid was then added to the solution. Upon completion of addition, the mixture was stirred at ambient temperature for about 18 hours. After this time, the methanol was removed from the mixture under reduced pressure, leaving an aqueous residue. The residue was washed with three portions of diethyl ether, then the pH of the residue was adjusted to about 8-9 by the addition of solid sodium carbonate. The mixture was then extracted with methylene chloride, and the extract was dried with sodium sulfate. The mixture was filtered and the filtrate was concentrated under reduced pressure to a residue. The residue was again treated with aqueous 4N hydrochloric acid, and the mixture was washed with diethyl ether. The pH of the aqueous layer was adjusted to about 8-9 by the addition of solid sodium carbonate. The mixture was then extracted with methylene chloride, and the extract was dried with sodium sulfate. The mixture was filtered and the filtrate was concentrated under reduced pressure, yielding about 0.5 gram of subject compound. The NMR spectrum was consistent with the proposed structure.

1. additionUpon completion of addition
2. additionwas added in one portion
3. additionUpon completion of addition
4. stirringthe reaction mixture was stirred at ambient temperature for about 18 hours
5. additionAfter this time, the reaction mixture was poured into a separatory funnel
6. customThe organic layer was separated
7. extractionthe aqueous layer was extracted with two portions of methylene chloride
8. dry with materialThe combined extracts and organic layer were dried with sodium sulfate
9. filtrationfiltered
10. concentrationThe filtrate was concentrated under reduced pressure to a residue
11. dissolutionThe residue was dissolved in methanol
12. additionaqueous 4N hydrochloric acid was then added to the solution
13. additionUpon completion of addition
14. stirringthe mixture was stirred at ambient temperature for about 18 hours
15. customAfter this time, the methanol was removed from the mixture under reduced pressure
16. customleaving an aqueous residue
17. washThe residue was washed with three portions of diethyl ether
18. additionthe pH of the residue was adjusted to about 8-9 by the addition of solid sodium carbonate
19. extractionThe mixture was then extracted with methylene chloride
20. dry with materialthe extract was dried with sodium sulfate
21. filtrationThe mixture was filtered
22. concentrationthe filtrate was concentrated under reduced pressure to a residue
23. additionThe residue was again treated with aqueous 4N hydrochloric acid
24. washthe mixture was washed with diethyl ether
25. additionThe pH of the aqueous layer was adjusted to about 8-9 by the addition of solid sodium carbonate
26. extractionThe mixture was then extracted with methylene chloride
27. dry with materialthe extract was dried with sodium sulfate
28. filtrationThe mixture was filtered
29. concentrationthe filtrate was concentrated under reduced pressure

ORD record

ord-6fd9008528a6416893b050aa21ab580a

Source dataset

uspto-grants-2008_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07417057B2