تفاعل #6660

معادلة التفاعل

(−)-tramadol

potassium hydride

thiophenol

→

O-desmethyl tramadol

المذيبات

diethylene glycol

Diethylene glycol

diethylene glycol

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةbeing maintained at <50° C
2. 2
   أخرىThe final reaction mixture
3. 3
   درجة الحرارةwas heated slowly
4. 4
   درجة الحرارةto reflux for 45 minutes
5. 5
   درجة الحرارةThe mixture was cooled
6. 6
   أخرىquenched into water
7. 7
   استخلاصthe mixture was extracted with ethyl ether
8. 8
   استخلاصthe resulting mixture was extracted 5 more times with methylene chloride
9. 9
   أخرىThe extract was dried
10. 10
    أخرىthe methylene chloride was evaporated

الإجراء التجريبي

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).

المصدر