Isopropylamine → (S)-Metoprolol

Participants

Reaction Steps

A solution of 290 mg of (+)-4-(2-methoxyethyl)-phenyl glycidyl ether of Example 1 in 6.2 ml of dried ethanol containing 1.84 ml of isopropylamine was heated at reflux for 3 hours after which the sovents were removed by evaporation The resulting oil was dissolved in 10 ml of methylene chloride and the solution was extracted with 10 ml of 0.2N HCl which was then washed twice with 10 ml of methylene chloride. The acid layer was made basic with 3 ml of 2N NaOH and the product was extracted with 10 ml of methylene chloride. The methylene chloride extract was dried over Na2SO4 and the solvent was evaporated to obtain a sticky solid. The product was crystallized from hexane to obtain 260 mg of (-)metoprolol having a [α]D25 =-5.46° (c=1.01 in ethanol) and melting at 42-45° C. (±)-metoprolol melting at 49-51° C., prepared chemically was, as expected, optically inactive. The pmr and mass spectra of (-)-metoprolol (FIGS. 2 and 3) and (±)-metoprolol (not shown) were consistent with the required structure and were indistinguishable from the pmr spectrum of (±)-meto prolol (melting at 48.5-50.5° C.) extracted from a commercial sample of metoprolol tartrate.

Provenance & Evidence