反应详情

温度

120 °C

A mixture of 4-cyano-piperidine-1-carboxylic acid benzyl ester (0.73 g, 3.0 mmol), sodium azide (0.39 g, 6.0 mmol) and zinc bromide (0.33 g, 1.5 mmol) in 2-propanol (5 mL) and water (10 mL) was stirred at 120° C. for 3 days into a pressure tube. The reaction mixture was then partitioned between aqueous 3.0N HCl (1.5 mL) and ethyl acetate and then stirred vigorously until 2 clear phases were obtained. Aqueous layer was then extracted with ethyl acetate and combined ethyl acetate layers dried over Na2SO4, filtered, and the solvent evaporated in vacuo to yield a crude residue. The residue was dissolved in ethyl acetate (10 mL) and washed with 0.25N aqueous sodium hydroxide. Aqueous layer was acidified to pH=1 with aqueous 3.0N HCl and extracted with ethyl acetate. Ethyl acetate layer was dried over Na2SO4, filtered, and the solvent evaporated in vacuo to yield a crude gum. The gum was purified via flash chromatography (4% methanol in dichloromethane) to yield 4-(1H-Tetrazol-5-yl)-piperidine-1-carboxylic acid benzyl ester as a gum (1.14 g, 66%).

1. customThe reaction mixture was then partitioned between aqueous 3.0N HCl (1.5 mL) and ethyl acetate
2. stirringstirred vigorously until 2 clear phases
3. customwere obtained
4. extractionAqueous layer was then extracted with ethyl acetate and combined ethyl acetate layers
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. customthe solvent evaporated in vacuo
8. customto yield a crude residue
9. washwashed with 0.25N aqueous sodium hydroxide
10. extractionextracted with ethyl acetate
11. dry with materialEthyl acetate layer was dried over Na2SO4
12. filtrationfiltered
13. customthe solvent evaporated in vacuo
14. customto yield a crude gum
15. customThe gum was purified via flash chromatography (4% methanol in dichloromethane)