Hydride → (S)-3-Chloro-1-(thiophen-2-yl)propan-1-ol

Participants

Reaction Steps

In this example, thiophene is used as the starting material to be acylated by Friedel-Crafts reaction so as to form 3-chloro-1-(2-thienyl)-propanone. Hydride reduction of this propanone forms racemic 3-chloro-1-(2-thienyl)-propan-1-ol. Racemic 3-chloro-1-(2-thienyl)-propan-1-ol is then resolved via enzymatic transesterification to form (S)-(−)-3-chloro-1-(2-thienyl)-propan-1-ol. Subsequently, the resulting chiral chloropropanol is aminated to form (S)-(−)-3-methylamino-1-(2-thienyl)-propan-1-ol with methylamine. In this process, the yield of enzymatic resolution is very low (35%). In addition, large excess, 20 equivalents, of methylamine is required for the amination reaction and the overall yield is low (24%), which renders this process economically less competitive.

Provenance & Evidence