Synthesis of all of the stereoisomers of β3-adrenoceptor antagonist SR 59230 based on the spontaneous resolution of 3-(2-ethylphenoxy)propane-1,2-diol

Racemic 3-(2-ethylphenoxy)propane-1,2-diol 2 has been effectively resolved into ( S )- and ( R )-enantiomers by a preferential crystallization procedure. Non-racemic diols 2 , obtained via a Mitsunobu reaction, have been converted into the non-racemic 1,2-epoxy-3-(2-ethylphenoxy)propanes ( S )- and ( R )- 5 and then into non-racemic 3-(2-ethylphenoxy)-1(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanols 1 . The characteristics of all four stereoisomers, ( S , S )- 1 (SR 59230), ( R , R )- 1 (SR 59483), ( R , S )- 1 and ( S , R )- 1 (SR 59231) and their hydrogen oxalates with a 1:1 composition have been presented. The crystalline oxalates ( S , S )- 1 ·C 2 H 2 O 4 (SR 59230A) and ( R , S )- 1 ·0.5C 2 H 2 O 4 were studied by single crystal X-ray diffraction.