Sulfuric Acid → (R)-Aminoglutethimide

Participants

Reaction Conditions

Reaction Steps

4-(4-Aminophenyl)-4-cyanohexanoic acid (Example 9; 1.8 g, 7.7 mmol), enriched in the (R)-enantiomer, was dissolved in glacial acetic acid (6.0 ml) contained in a 25 ml round-bottomed flask. The resulting mixture was heated to 60° C. with the aid of an oil bath followed by dropwise addition of conc. H2SO4 (3.0 ml). The solution was then heated to 100° C. and maintained there for 30 minutes before pouring onto ice (100 g). The pH is adjusted to 6 using 5M NaOH followed by extraction with dichloromethane (3×200 ml). The extracts were pooled, dried (over MgSO4) and concentrated under reduced pressure, giving (R)-aminoglutethimide (1.75 g, 97%) as a brown oil. Chiral HPLC analysis (Chiralcel OJ column; mobile phase 1:1 n-heptane-isopropanol) indicated an ee of 78%.

Provenance & Evidence