Hydrochloric Acid → Hydrochloric Acid

Participants

Reaction Steps

Propionyl chloride (1.3 equivalents) was added to a 0.4M methylene chloride solution of 6 in a glass stoppered RB flask at RT. A mild exotherm developed and analysis by LC at the end of 40 minutes showed 90% sufentanil 7 with about 7% starting material 6. About 8% by weight of triethylamine was then added and stirred for another 40 minutes at RT. LC showed 95% product with no trace of starting material 6. The mixture was then quenched with an excess of dilute ammonium hydroxide and the lower methylene chloride layer was separated, washed with water and dried. Evaporation of methylene chloride gave a yellow powder which by LC amounted to 95% sufentanil 7. This was converted to HCl salt by dissolving in ether (250 ml) and stirring with 4N HCl [100 ml]. The precipitated HCl salt was filtered off, washed with ether and air-dried. Recrystallization from water (6 ml for every gm of Sufentanil.HCl) gave sufentanil HCl (19.6 g) as white paste with LC purity of 99.50%. The isolated yield of the pure HCl salt was 85%. H1NMR (CDCl3): δ7.25-6.85 (m,8H), 4.05 (s,2H), 3.35 (s,3H), 3.14-1.56 (m,14H), 0.95 (t,3H).

Provenance & Evidence