反应详情

A slurry of lithium aluminum hydride (LiAlH4) (7.48 g, 197 mmol) in 180 mL of tetrahydrofuran (THF) is cooled to 0° C. and treated with aluminum chloride (AlCl3) (8.76 g, 65.7 mmol) in 180 mL of diethyl ether. The reaction was stirred for 30 minutes and the 2-(1,4dioxaspiro[4.5]dec-8-yl)-1-[4-(2-pyridinyl)-1-piperazinyl]-ethanone (22.7 g, 65.7 mmol) was added in portions over 1 hour. The reaction is allowed to stir for 18 hours and is quenched with 8 mL of water and 18 mL of a 50% sodium hydroxide (NaOH) solution. The reaction is stirred for 1 hour and filtered through a pad of Celite. The filter cake is washed with 300 mL of diethyl ether. The combined organic extracts are concentrated to give a white solid which is dissolved in a 230 mL of a 1:1 mixture of acetone and 10% aqueous hydrochloric acid (HCl) solution. After stirring at room temperature for 60 hours, the acetone is removed under reduced pressure, and the pH of the reaction mixture is adjusted to pH 9 with concentrated ammonium hydroxide solution. The aqueous mixture is extracted with two 250 mL portions of chloroform, and the combined organic fractions are dried with sodium sulfate. The solvents are removed under reduced pressure, and the residue is triturated with diethyl ether to give 14.3 g 4-[2-[4-(2-pyridinyl)-1-piperazinyl]ethyl]-cyclohexanone as a white solid.

1. stirringto stir for 18 hours
2. customis quenched with 8 mL of water and 18 mL of a 50% sodium hydroxide (NaOH) solution
3. stirringThe reaction is stirred for 1 hour
4. filtrationfiltered through a pad of Celite
5. washThe filter cake is washed with 300 mL of diethyl ether
6. concentrationThe combined organic extracts are concentrated
7. customto give a white solid which
8. stirringAfter stirring at room temperature for 60 hours
9. customthe acetone is removed under reduced pressure
10. extractionThe aqueous mixture is extracted with two 250 mL portions of chloroform
11. dry with materialthe combined organic fractions are dried with sodium sulfate
12. customThe solvents are removed under reduced pressure
13. customthe residue is triturated with diethyl ether