Reaktion #57117

Reaktionsgleichung

cyclohexanone

tert-butyl 4-(2-Pyridin-2-yl-ethyl)-piperazine-1-carboxylate

n-butyllithium

→

tert-butyl 4-[2-(1-hydroxy-cyclohexyl)-2-pyridin-2-yl-ethyl]-piperazine-1-carboxylate

Ausbeute 78.0%

Lösungsmittel

tetrahydrofuran

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe reaction was stirred at −78° C. for 45 min
2. 2
   Sonstigeafter which time the reaction was then quenched by the addition of a saturated aqueous solution of sodium bicarbonate
3. 3
   Sonstigethe tetrahydrofuran was removed in vacuo
4. 4
   SonstigeThe resulting residue was partitioned between water and ethyl acetate
5. 5
   Sonstigethe layers were separated
6. 6
   ExtraktionThe aqueous layer was extracted with ethyl acetate (3×30 mL)
7. 7
   Trocknenthe combined organic extracts were dried over magnesium sulfate
8. 8
   Einengenconcentrated in vacuo
9. 9
   Sonstigethe product was purified via Biotage Horizon (FLASH 25 M, silica, gradient from 0% methanol/EtOAc to 10% methanol/EtOAc)

Vorschrift

A solution of tert-butyl 4-(2-Pyridin-2-yl-ethyl)-piperazine-1-carboxylate (466 mg, 1.60 mmol) in dry tetrahydrofuran (6 mL) under nitrogen was cooled to −78° C. and treated dropwise with a solution of n-butyllithium (2.5 M in hexanes, 0.70 mL, 1.75 mmol). The resulting solution was stirred at −78° C. for 1 h. The reaction was then treated with a solution of cyclohexanone (174 mg, 1.77 mmol) in dry tetrahydrofuran (0.8 mL). The reaction was stirred at −78° C. for 45 min, after which time the reaction was then quenched by the addition of a saturated aqueous solution of sodium bicarbonate, and the tetrahydrofuran was removed in vacuo. The resulting residue was partitioned between water and ethyl acetate and the layers were separated. The aqueous layer was extracted with ethyl acetate (3×30 mL), and the combined organic extracts were dried over magnesium sulfate and concentrated in vacuo and the product was purified via Biotage Horizon (FLASH 25 M, silica, gradient from 0% methanol/EtOAc to 10% methanol/EtOAc) to yield 484 mg (78%) tert-butyl 4-[2-(1-hydroxy-cyclohexyl)-2-pyridin-2-yl-ethyl]-piperazine-1-carboxylate as a colorless oil.

Quelle