(S)-mandelic acid → 3-[4-(2-(Cyclopropylmethoxy)ethyl)phenoxy]-2-hydroxypropylamine

Participants

Reaction Steps

(±)-3-[4-(2-(Cyclopropylmethoxy)ethyl)phenoxy]-2-hydroxypropylamine (25 g) was dissolved in hot water (200 ml) and methanol (50 ml). To this solution was added, with vigorous stirring, a solution of L-(+)-mandelic acid (14.35 g) in hot water (200 ml). The mixture was stirred for five minutes, cooled and seeded to give crystals. These were collected and recrystallised three times from hot water to afford a mandelate salt of 3-[4-(2-(cyclopropylmethoxy)ethyl)phenoxy]-2-hydroxypropylamine (5.04 g). To part of this compound (4.54 g) in chloroform (75 ml) was added 15% sodium carbonate solution (75 ml) and the two phase mixture was vigorously stirred at room temperature for one hour. The two layers were separated, the aqueous layer washed with chloroform (3×25 ml) and the organic layer and chloroform washings were combined, dried and evaporated under reduced pressure to give a residue (2.81 g). This residue was dissolved in hot acetonitrile (25 ml), filtered, evaporated to low volume and cooled to afford (-)-3-[4-(2-(cyclopropylmethoxy)ethyl)phenoxy]-2-hydroxypropylamine (2.05 g), [α]D25 =-17.77° [concentration 1.1% in ethanol:water:concentrated HCl (17:2:1)]: nuclear magnetic resonance spectrum consistent with racemic material; identical by chromatography.

Provenance & Evidence