Reaktion #62326

Reaktionsgleichung

2-(2-bromoethoxy)-tetrahydropyran

ammonium chloride

3-[(E)-2-(4-fluorophenyl)-vinyl]-4-hydroxy-1H-indazole-1,5-dicarboxylic acid 1-tert-butyl ester 5-ethyl ester

2-(2-bromoethoxy)-tetrahydropyran

cesium carbonate

2-(2-bromoethoxy)-tetrahydropyran

cesium carbonate

→

title compound

Ausbeute 56.5%

3-[(E)-2-(4-Fluorophenyl)-vinyl]-4-[2-(tetrahydropyran-2-yloxy)-ethoxy]-1H-indazole-1,5-dicarboxylic acid 1-tert-butyl Ester 5-ethyl ester

Ausbeute 56.5%

Lösungsmittel

N,N-dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGstirred at 50° C. for 17 hours
2. 2
   workup.STIRRINGstirred for 3 hours at room temperature and for 2 hours at 50° C.
3. 3
   workup.STIRRINGfurther stirred at 50° C. for 4 hours
4. 4
   Extraktionextracted twice with ethyl acetate
5. 5
   Waschenthe resultant organic layer was washed once with saturated brine
6. 6
   Trocknendried over magnesium sulfate
7. 7
   SonstigeThe solvent was evaporated
8. 8
   Sonstigethe crude product was purified
9. 9
   Sonstigeseparated by silica gel column chromatography

Vorschrift

To a solution of 200 mg of 3-[(E)-2-(4-fluorophenyl)-vinyl]-4-hydroxy-1H-indazole-1,5-dicarboxylic acid 1-tert-butyl ester 5-ethyl ester in 13 mL of N,N-dimethylformamide were added 196.5 mg of 2-(2-bromoethoxy)-tetrahydropyran and 306.3 mg of cesium carbonate, stirred for 1 hour and 30 minutes at room temperature, stirred at 50° C. for 17 hours, added with 196.5 mg of 2-(2-bromoethoxy)-tetrahydropyran and 306.3 mg of cesium carbonate, stirred for 3 hours at room temperature and for 2 hours at 50° C., added with 554 mg of 2-(2-bromoethoxy)-tetrahydropyran, and further stirred at 50° C. for 4 hours. Then, the reaction solution was added saturated aqueous ammonium chloride, extracted twice with ethyl acetate, and the resultant organic layer was washed once with saturated brine and dried over magnesium sulfate. The solvent was evaporated, and the crude product was purified and separated by silica gel column chromatography, to afford 147 mg of the title compound as a colorless oil.

Quelle