Réaction #57117

Équation de réaction

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

Rendement 78.0%

Solvants

tetrahydrofuran

tetrahydrofuran

Conditions de réaction

Traitement

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

Mode opératoire

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.

Source