A scalable synthesis of (R)-3-(2-aminopropyl)-7-benzyloxyindole via resolution

(+/-)-3-(2-Aminopropyl)-7-benzyloxyindole 1. assembled from 7-benzyloxyindole 3 in 59% overall yield, is resolved with O.O'-di-p-toluoyl L-(2R,3R)-tartaric acid 7 into (R)-1. a key intermediate of AJ-9677 2 (selective adrenaline beta(3)-agonist) in 99.5% e.e. and 36% overall yield. The unwanted enantiomer (S)-1 (61.9% e.e.: recovered in 57% yield from the crystallization filtrate) can be reused in another round of resolution after its enantiomeric purity is lowered to 3.7% by Raney Co treatment under a hydrogen atmosphere. (C) 2002 Elsevier Science Ltd. All rights reserved.