Reacción #57117

Ecuación de reacción

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

Rendimiento 78.0%

Disolventes

tetrahydrofuran

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

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

Procedimiento

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.

Fuente