Reaktion #60510

Reaktionsgleichung

sodium hydrogencarbonate

ethyl acetate

trans-(2-{4-[2-(3,3,5,5-tetramethylcyclohexyl)phenyl]piperazin-1-ylmethyl}cyclopropyl)methanol

diethylaminosulfur trifluoride

→

trans-1-(2-fluoromethylcyclopropylmethyl)-4-[2-(3,3,5,5-tetramethylcyclohexyl)phenyl]piperazine

Ausbeute 28.2%

Lösungsmittel

water

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added
2. 2
   workup.STIRRINGthe mixture was stirred
3. 3
   Extraktionextraction
4. 4
   WaschenThe separated organic layer was washed with brine
5. 5
   Trocknendried over anhydrous sodium sulfate
6. 6
   FiltrationThe desiccant was filtered off
7. 7
   Einengenthe filtrate was concentrated under reduced pressure
8. 8
   SonstigeThe resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane)

Vorschrift

To a solution of trans-(2-{4-[2-(3,3,5,5-tetramethylcyclohexyl)phenyl]piperazin-1-ylmethyl}cyclopropyl)methanol (60 mg, 0.156 mmol) produced in Example (92a) in dichloromethane (5 mL) was added diethylaminosulfur trifluoride (DAST) (0.052 mL, 0.394 mmol), followed by stirring for 2 hours at room temperature under a nitrogen atmosphere. The reaction mixture was cooled at an external temperature of 0° C., saturated aqueous solution of sodium hydrogencarbonate was added, and the mixture was stirred. Then, ethyl acetate and water were added thereto and extraction was performed with ethyl acetate. The separated organic layer was washed with brine and then dried over anhydrous sodium sulfate. The desiccant was filtered off and the filtrate was concentrated under reduced pressure. The resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane) to give 17 mg of trans-1-(2-fluoromethylcyclopropylmethyl)-4-[2-(3,3,5,5-tetramethylcyclohexyl)phenyl]piperazine as a colorless oil.

Quelle