proline dl-form → HCID 53253006, compound

A mixture of 5.40 g of (3,3,4,4,5,5,6,6,6-nonafluorohexylsulfonyl)acetonitrile, 60 ml of toluene, 0.18 g of DL-proline and 2.77 g of 1,4-cyclohexanedione monoethylene ketal was heated and stirred for 3 hours under the reflux condition. After 40 ml of toluene was distilled off, the reaction mixture was cooled to room temperature. The mixture was cooled to 0° C. and then 0.61 g of sodium borohydride was added thereto. To the reaction mixture was added 3 ml of N,N-dimethylformamide. The mixture was stirred at room temperature for 6 hours and then cooled to 0° C. Thereto 50 ml of water and 50 ml of ethyl acetate were added. While the reaction mixture was stirred, 20 ml of an aqueous 1N hydrochloric acid solution was added dropwise, followed by extraction with 100 ml of ethyl acetate twice. An organic layer was washed with 100 ml of an aqueous saturated sodium hydrogen carbonate solution, 100 ml of an aqueous saturated sodium chloride solution and 100 ml of water, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was dissolve to 14 ml of acetic acid and 6 ml of water. The mixture was heated to 100° C. and stirred for 8 hours. After the reaction mixture was cooled to room temperature, 100 ml of ethyl acetate was added thereto. The mixture was added slowly into 100 ml of an aqueous saturated sodium hydrogen carbonate solution. The solution was stirred for 1 hour, followed by extraction with 100 ml of ethyl acetate twice. Organic layers were combined, washed with 100 ml of an aqueous saturated sodium hydrogen carbonate solution and 100 ml of an aqueous saturated sodium chloride solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 2.94 g of 2-(4-oxocyclohexyl)-2-(3,3,4,4,5,5,6,6,6-nonafluorohexylsulfonyl)acetonitrile (hereinafter, referred to as the present compound (62)) represented by the formula:

1. temperaturewas heated
2. distillationAfter 40 ml of toluene was distilled off
3. temperatureThe mixture was cooled to 0° C.
4. addition0.61 g of sodium borohydride was added
5. additionTo the reaction mixture was added 3 ml of N,N-dimethylformamide
6. stirringThe mixture was stirred at room temperature for 6 hours
7. temperaturecooled to 0° C
8. additionThereto 50 ml of water and 50 ml of ethyl acetate were added
9. stirringWhile the reaction mixture was stirred
10. addition20 ml of an aqueous 1N hydrochloric acid solution was added dropwise
11. extractionfollowed by extraction with 100 ml of ethyl acetate twice
12. washAn organic layer was washed with 100 ml of an aqueous saturated sodium hydrogen carbonate solution, 100 ml of an aqueous saturated sodium chloride solution and 100 ml of water
13. dry with materialdried over sodium sulfate
14. filtrationfiltered
15. concentrationconcentrated under reduced pressure
16. dissolutionThe residue was dissolve to 14 ml of acetic acid and 6 ml of water
17. temperatureThe mixture was heated to 100° C.
18. stirringstirred for 8 hours
19. temperatureAfter the reaction mixture was cooled to room temperature
20. addition100 ml of ethyl acetate was added
21. additionThe mixture was added slowly into 100 ml of an aqueous saturated sodium hydrogen carbonate solution
22. stirringThe solution was stirred for 1 hour
23. extractionfollowed by extraction with 100 ml of ethyl acetate twice
24. washwashed with 100 ml of an aqueous saturated sodium hydrogen carbonate solution and 100 ml of an aqueous saturated sodium chloride solution
25. dry with materialdried over sodium sulfate
26. filtrationfiltered
27. concentrationconcentrated under reduced pressure

ORD record

ord-c48ff6ddf6d54c0fa20157c0f17618fb

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08247596B2