반응 #216582

ord-9bcd66430d9a456faead55416dd089d9

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도being maintained at <50° C
  2. 2
    기타The final reaction mixture
  3. 3
    온도was heated slowly
  4. 4
    온도to reflux for 45 minutes
  5. 5
    온도The mixture was cooled
  6. 6
    기타quenched with water
  7. 7
    추출the mixture was extracted with ethyl ether
  8. 8
    추출the resulting mixture was extracted 5 more times with methylene chloride
  9. 9
    기타The extract was dried
  10. 10
    기타the methylene chloride was evaporated

실험 절차

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 quenched with 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. The title compound (4.6 g) was distilled (Kugelrohr), was dissolved in tetrahydrofuran and treated with an ethanol/HCl solution to give 2.3 g of the hydrochloride salt. The salt was recrystallized from ethanol/ethyl ether and dried to yield 1.80 g of the salt of the (-) enantiomer of O-desmethylated tramadol (mp. 242°-3° C.), [α]D25 =-32.9 (C=1, EtOH).

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US05468744uspto-grants-1995_11