Reaktion #42042

Reaktionsgleichung

ammonium chloride

potassium t-butoxide

4-fluoro-3-trifluoromethylbenzonitrile

1-methyl-4-hydroxypiperidine

→

objective compound

Ausbeute 64.8%

4-(1-methylpiperidin-4-yloxy)-3-trifluoromethylbenzonitrile

Ausbeute 64.8%

Lösungsmittel

water

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGfurther the mixture was stirred for 30 minutes
2. 2
   workup.STIRRINGthe mixture was stirred
3. 3
   Temperaturunder cooling in a dry ice/acetone bath
4. 4
   Sonstigethe solution prepared earlier
5. 5
   workup.ADDITIONwas added dropwise at the internal temperature of −70° C
6. 6
   workup.ADDITIONAfter adding dropwise
7. 7
   workup.STIRRINGthe reaction solution was stirred overnight
8. 8
   Temperaturcooled
9. 9
   workup.DISTILLATIONthe solvent was distilled off under reduced pressure
10. 10
    ExtraktionThe residue was subjected to extraction with ethyl acetate twice
11. 11
    WaschenThe extracts were washed in turn with water and saturated saline
12. 12
    Trocknendried over anhydrous magnesium sulfate
13. 13
    workup.DISTILLATIONthe solvent was distilled off under reduced pressure
14. 14
    SonstigeThe residue was purified by silica gel column chromatography

Vorschrift

6.68 g of potassium t-butoxide was suspended in 40 ml of anhydrous tetrahydrofuran and a solution of 6.85 g of 1-methyl-4-hydroxypiperidine in 20 ml of anhydrous tetrahydrofuran was added dropwise over 35 minutes while stirring under ice-water cooling and further the mixture was stirred for 30 minutes. On the other hand, 7.50 g of 4-fluoro-3-trifluoromethylbenzonitrile was dissolved in 40 ml of anhydrous tetrahydrofuran, the mixture was stirred under cooling in a dry ice/acetone bath, and the solution prepared earlier was added dropwise at the internal temperature of −70° C. After adding dropwise, the reaction solution was stirred overnight while naturally heating up to room temperature. The reaction solution was ice-cooled, an aqueous saturated ammonium chloride solution and water were added thereto, and then the solvent was distilled off under reduced pressure. The residue was subjected to extraction with ethyl acetate twice. The extracts were washed in turn with water and saturated saline and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to obtain 7.31 g of the objective compound as colorless crystals.

Quelle