proline dl-form → HCID 67251467, compound

A mixture of 4.02 g of (3,3,3-trifluoropropylsulfonyl)acetonitrile, 100 ml of toluene, 0.23 g of DL-proline and 3.32 g of 1,4-cyclohexanedione monoethylene ketal was heated and stirred for 3 hours under the reflux condition. After 20 ml of toluene was distilled off, the reaction mixture was cooled to room temperature. To the reaction mixture was added 100 ml of tetrahydrofuran. The mixture was cooled to 0° C. and then 1.01 g of sodium borohydride was added thereto. The mixture was stirred at room temperature for 6 hours and then cooled to 0° C. Thereto 100 ml of water and 100 ml of ethyl acetate were added. While the reaction mixture was stirred, 100 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 subjected to silica gel column chromatography to obtain 5.45 g of 2-(1,4-dioxaspiro[4.5]dec-8-yl)-2-(3,3,3-trifluoropropylsulfonyl)acetonitrile (hereinafter referred to as the present compound (27)) represented by the following formula (27).

1. temperaturewas heated
2. distillationAfter 20 ml of toluene was distilled off
3. additionTo the reaction mixture was added 100 ml of tetrahydrofuran
4. temperatureThe mixture was cooled to 0° C.
5. addition1.01 g of sodium borohydride was added
6. stirringThe mixture was stirred at room temperature for 6 hours
7. temperaturecooled to 0° C
8. additionThereto 100 ml of water and 100 ml of ethyl acetate were added
9. stirringWhile the reaction mixture was stirred
10. addition100 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

ORD record

ord-a3ed9219442a4c23baa8bd5c0d057ee0

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08247596B2