Dimethylformamide → 1-Amino-3-(3,4-difluorophenyl)piperidin-2-one

Sodium hydride (containing mineral oil at 40%, 0.48 g) was added to a solution of methyl (3,4-difluorophenyl)acetate (CAS #210530-71-5, 2.04 g) in DMF (30 mL) at 0° C., and the reaction solution was stirred at room temperature for 10 minutes. 1-chloro-3-iodopropane (1.3 mL) was added to the reaction solution at 0° C., and the reaction solution was stirred at room temperature for two hours. A saturated ammonium chloride solution was added to the reaction solution, followed by extraction with ethyl acetate. The resulting extract was washed with a saturated sodium chloride solution. The resulting organic layer was dried over magnesium sulfate and then concentrated under reduced pressure. Hydrazine monohydrate (5.5 g) was added to a solution of the resulting residue in ethanol (50 mL) at room temperature, and the reaction solution was stirred at 80° C. for seven hours. The reaction solution was left to cool to room temperature and concentrated under reduced pressure. A saturated sodium bicarbonate solution was added to the residue, followed by extraction with chloroform. The resulting extract was dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system, then ethyl acetate-methanol system) to obtain 1.42 g of the title compound. The property values of the compound are as follows.

1. stirringthe reaction solution was stirred at room temperature for two hours
2. extractionfollowed by extraction with ethyl acetate
3. extractionThe resulting extract
4. washwas washed with a saturated sodium chloride solution
5. dry with materialThe resulting organic layer was dried over magnesium sulfate
6. concentrationconcentrated under reduced pressure
7. additionHydrazine monohydrate (5.5 g) was added to a solution of the resulting residue in ethanol (50 mL) at room temperature
8. stirringthe reaction solution was stirred at 80° C. for seven hours
9. waitThe reaction solution was left
10. temperatureto cool to room temperature
11. concentrationconcentrated under reduced pressure
12. additionA saturated sodium bicarbonate solution was added to the residue
13. extractionfollowed by extraction with chloroform
14. extractionThe resulting extract
15. dry with materialwas dried over magnesium sulfate
16. concentrationconcentrated under reduced pressure
17. customThe residue was purified by silica gel column chromatography (
18. washelution solvent

ORDレコード

ord-6a6d79f1b65d44ef8c85cafd2ec3e6ec

出典データセット

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07897632B2