反应 #6660

反应方程式

(−)-tramadol

potassium hydride

thiophenol

→

O-desmethyl tramadol

溶剂

diethylene glycol

Diethylene glycol

diethylene glycol

反应条件

后处理

1. 1
   温度being maintained at <50° C
2. 2
   其他The final reaction mixture
3. 3
   温度was heated slowly
4. 4
   温度to reflux for 45 minutes
5. 5
   温度The mixture was cooled
6. 6
   其他quenched into water
7. 7
   萃取the mixture was extracted with ethyl ether
8. 8
   萃取the resulting mixture was extracted 5 more times with methylene chloride
9. 9
   其他The extract was dried
10. 10
    其他the methylene chloride was evaporated

实验过程

First, O-desmethyl tramadol was prepared as set forth hereinafter. Diethylene glycol (125 mL) was added with cooling to potassium hydride (9.5 g) with the temperature being maintained at <50° C. To the solution was added thiophenol (10 mL) dissolved in diethylene glycol (25 mL), and then (−)-tramadol as the free base (9.3 g) in diethylene glycol (50 mL) was added. The final reaction mixture was heated slowly to reflux for 45 minutes. The mixture was cooled and then quenched into water. The pH was adjusted to about 3, and the mixture was extracted with ethyl ether. The pH was readjusted to about 8 and the resulting mixture was extracted 5 more times with methylene chloride. The extract was dried and the methylene chloride was evaporated to yield 4.6 g of the title compound as an oil. The oil was distilled (Kugelrohr), dissolved in tetrahydrofuran, treated with an ethanol/HCl solution to give 2.3 g of the salt. The salt was recrystallized from ethanol/ethyl ether and dried to yield 1.80 g of the salt of the (−) enantiomer of O-desmethyl tramadol (mp. 242°-3° C.), [α]D25=−32.9 (C=1, EtOH).

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