反应详情

A 5-liter, 3-neck flask was equipped with mechanical stirring, a reflux condenser, and a powder addition funnel. Sodium bicarbonate (840 g, 10 mmol) was added via the powder funnel while stirring, then water (ca. 300-400 mL) was gradually added while vigorously stirring to form a thick, uniform slurry. The flask was then placed in an ice bath, and a solution of 4-hydroxypiperidine (506 g, 5.00 mol) in CH2Cl2 (1.0 L) was added, and the contents were vigorously mixed while cooling. A solution of cyanogen bromide (640 g, 6.0 mol) in CH2Cl2 (600 mL) was added in a dropwise fashion over 2 h, and stirring was continued for an additional 30 min. The ice bath was removed, and the mechanical stirrer was replaced by a magnetic stirrer, and the reaction mixture was stirred for 16 h. The flask was once again placed under mechanical stirring, and sodium carbonate (100 g) was added in order to ensure complete neutralization. MgSO4 (500 g) was added, and vigorous stirring was continued for 15 min. The resulting suspension was filtered, rinsing with CH2Cl2 (2.0 L). A light amber, viscous oil was obtained upon solvent removal to give 1-cyano-4-hydroxypiperidine (574 g, 91% yield. 1H NMR (CDCl3) δ 3.80 (m, 1 H), 3.39 (m, 2 H), 3.05 (m, 2 H), 1.87 (m, 2 H), 1.70 (br s, 1 H), 1.62 (m, 2 H), MS m/z 212.1 (M+).

1. customA 5-liter, 3-neck flask was equipped with mechanical stirring, a reflux condenser, and a powder addition funnel
2. stirringwhile vigorously stirring
3. customto form a thick, uniform slurry
4. customThe flask was then placed in an ice bath
5. additionthe contents were vigorously mixed
6. temperaturewhile cooling
7. stirringstirring
8. customThe ice bath was removed
9. customthe mechanical stirrer was replaced by a magnetic stirrer
10. stirringthe reaction mixture was stirred for 16 h
11. additionwas added in order
12. additionMgSO4 (500 g) was added
13. stirringvigorous stirring
14. waitwas continued for 15 min
15. filtrationThe resulting suspension was filtered
16. washrinsing with CH2Cl2 (2.0 L)
17. customA light amber, viscous oil was obtained upon solvent removal