Convenient and inexpensive synthesis of (1R,2R)-trans-1-amino-6-nitroindan-2-ol

Abstract

Racemic trans- 1-amino-6-nitroindan -2-ol (rac-1) has been prepared in five steps from inexpensive indene (7) in 96% overall yield. The key step was a direct nitration of the known trans-1-aminoindan-2ol (rac-9) which gave sulfuric acid mono- (rac-trans-1-amino-6-nitroindan-2-yl) ester (rac-10) in quantitative yield. The latter was quantitatively converted into rac-1 by treatment with aqueous 6 N HCl and then ammonia solutions. The same transformations of (1R,2R)-9 [prepared by deracernization of rac-9 with (-)-dibenzoyl-(L)-tartaric acid (DBT)] proceeded with- out loss of the optical activity. Deracernization of rac-1 applying (+)-(S)-(L)-mandelic acid (MA) furnished (1R,2R)-1 and (1S,2S)-1 in 34 and 17% yield, respectively, with e.e. greater than or equal to 98 and 97.6%, respectively. Procedures for recycling of the chiral auxiliaries DBT and MA are also described. The structures of key intermediates were confirmed by X-ray crystal structure analysis.