Sodium Iodide → 1-[4-Cyano-5-methyl-4-(2-cyano-5-thienyl)hexyl]-4-[2-(4-fluorophenoxy)ethyl]piperazine

温度

0 °C

4-Cyano-5-methyl-4-(2-cyano-5-thienyl)hexanol, 273 mg 1.10 mmol, was dissolved in acetonitrile 5.00 ml and cooled at 0° C. Triethylamine 0.16 ml and methane sulfonyl chloride 0.10 ml 1.21 mmol were added thereto and the temperature was raised to room temperature. After 1 hour, the mixture was partitioned by adding ether and brine. The organic layer was washed with aqueous saturated sodium bicarbonate, dried over magnesium sulfate anhydride and evaporated. A half about 0.55 mmol of the residues was dissolved in N,N-dimethylformamide 5.00 ml, and 500 mg 3.34 mmol of sodium iodide, 76.0 mg 0.55 mmol of potassium carbonate, and 202 mg 0.90 mmol of 1-[2-(4-fluorophenoxy)ethyl]piperazine were added thereto, and the mixture was heated at 60° C. Brine was added to the reaction mixture which was then extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate anhydride, and evaporated. The residue was purified by Chromatorex NH silica gel column chromatography (ethyl acetate/hexane system), whereby the title compound, 215 mg 0.47 mmol, 86.0%, was obtained as a yellow syrup.

1. temperaturethe temperature was raised to room temperature
2. customthe mixture was partitioned
3. additionby adding ether and brine
4. washThe organic layer was washed with aqueous saturated sodium bicarbonate
5. dry with materialdried over magnesium sulfate anhydride
6. customevaporated
7. temperaturethe mixture was heated at 60° C
8. extractionwas then extracted with ethyl acetate
9. washThe organic layer was washed with brine
10. dry with materialdried over magnesium sulfate anhydride
11. customevaporated
12. customThe residue was purified by Chromatorex NH silica gel column chromatography (ethyl acetate/hexane system), whereby the title compound, 215 mg 0.47 mmol, 86.0%
13. customwas obtained as a yellow syrup

ORDレコード

ord-ce599b00cccb4b2783ffb728be43d65a

出典データセット

uspto-grants-2004_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06737425B1