反应详情

DIBAL-H (6.9 ml, 10.35 mmol, 1.5 M in toluene) was added to a solution of ethyl [1-(3,4-dichlorobenzyl)piperidin-4-yl]acetate (1.9 g, 5.8 mmol) in dry toluene (60 ml) at −60° C. under nitrogen atmosphere. The reaction mixture was stirred at dry ice bath temperature for 0.5 h, quenched with saturated sodium bisulfite solution and then allowed to warm to room temperature. The aqueous layer was separated and basified with 2N sodium hydroxide to pH between 8-9 and the product was extracted with diethyl ether. The combined ether layers were washed with brine and dried over sodium sulfate. After concentration, the residue was dissolved in dry tetrahydrofuran (30 ml) and cooled to 0° C. Isopropyl magnesium chloride (2.0 M, 5.8 ml) was added dropwise and the resulting reaction mixture was allowed to warm to room temperature. After 0.5 h, the reaction mixture was quenched with water and extracted with diethyl ether. The ether layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified on silica gel column with 25% acetone, 25% dichloromethane in hexanes to give 1(RS)-[1-(3,4-dichlorobenzyl)piperidin-4-ylmethyl]-2-methylpropanol (0.75 g) as an oil.

1. customquenched with saturated sodium bisulfite solution
2. customThe aqueous layer was separated
3. extractionthe product was extracted with diethyl ether
4. washThe combined ether layers were washed with brine
5. dry with materialdried over sodium sulfate
6. concentrationAfter concentration
7. dissolutionthe residue was dissolved in dry tetrahydrofuran (30 ml)
8. temperaturecooled to 0° C
9. additionIsopropyl magnesium chloride (2.0 M, 5.8 ml) was added dropwise
10. customthe resulting reaction mixture
11. temperatureto warm to room temperature
12. waitAfter 0.5 h
13. customthe reaction mixture was quenched with water
14. extractionextracted with diethyl ether
15. washThe ether layer was washed with brine
16. dry with materialdried over sodium sulfate
17. concentrationconcentrated in vacuo
18. customThe residue was purified on silica gel column with 25% acetone, 25% dichloromethane in hexanes