Reaktion #60506

Reaktionsgleichung

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

[(1-ethoxycyclopropyl)oxy]trimethylsilane

sodium cyanotrihydroborate

acetic acid

→

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

Lösungsmittel

Ethyl acetate

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   Filtrationwas filtered through Celite
2. 2
   Einengenthe filtrate was concentrated
3. 3
   workup.ADDITIONWater was then added to the residue, extraction
4. 4
   Waschenthe organic layer was washed with 2N aqueous solution of sodium hydroxide and brine
5. 5
   TrocknenThe organic layer was dried over magnesium sulfate
6. 6
   Filtrationthe desiccant was filtered off
7. 7
   Einengenthe filtrate was concentrated
8. 8
   SonstigeThe resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane)

Vorschrift

To a solution of 1-[2-(3,3,5,5-tetramethylcyclohexyl)phenyl]piperazine (30 mg, 0.1 mmol) produced in Example (8b) in methanol (3 mL) were added [(1-ethoxycyclopropyl)oxy]trimethylsilane (105 mg, 0.6 mmol), sodium cyanotrihydroborate (28.3 mg, 0.45 mmol), acetic acid (60.1 mg, 1 mmol) and molecular sieves 3A (50 mg) in that order, followed by stirring for 5 hours and 30 minutes at an external temperature of 80° C. Ethyl acetate was added to the reaction mixture, which was filtered through Celite, and the filtrate was concentrated. Water was then added to the residue, extraction was performed with ethyl acetate, and the organic layer was washed with 2N aqueous solution of sodium hydroxide and brine. The organic layer was dried over magnesium sulfate, the desiccant was filtered off, and then the filtrate was concentrated. The resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane) to give 1-cyclopropyl-4-[2-(3,3,5,5-tetramethylcyclohexyl)phenyl]piperazine as a white solid. The obtained compound was dissolved in ethyl acetate, and a 4N solution of hydrogen chloride in ethyl acetate (0.040 mL, 0.160 mmol) was added. The solution was concentrated, and hexane was added to the obtained residue to produce a solid, which was then triturated by sonication. The supernatant hexane solution was removed and the resulting solid residue was dried under reduced pressure to give 37.7 mg of the title compound as a white solid.

Quelle