An efficient and promising method to prepare Ladostigil (TV3326) via asymmetric transfer hydrogenation catalyzed by Ru–Cs-DPEN in an HCOONa–H2O–surfactant system

The enantiopure multi-functional anti Alzheimer’s drug, Ladostigil (TV3326), was prepared by using asymmetric transfer hydrogenation (ATH) as a key step catalyzed by Ru–Cs-DPEN in an HCOONa–H2O–surfactant system. Good chemical yields with high enantiomeric excess were obtained and the catalyst could be recycled another five times.

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(S)-3-Hydroxy-2,3-dihydro-1H-inden-5-yl ethyl(methyl)carbamateC13H17NO3ee: 98%[α]D20=+27.2 (c 2.38, CHCl3)Source of chirality: asymmetric transfer hydrogenationAbsolute configuration: (S)

(R)-3-(Prop-2-ynylamino)-2,3-dihydro-1H-inden-5-yl ethyl(methyl)carbamateC16H20N2O2ee: 89%[α]D20=+1.1 (c 1.46, CHCl3)Source of chirality: the precursorAbsolute configuration: (R)

(R)-3-(Prop-2-ynylamino)-2,3-dihydro-1H-inden-5-yl ethyl(methyl)carbamate hemi((2R,3R)-2,3-dihydroxysuccinate)C36H46N4O10ee: 99%[α]D20=+11.8 (c 1.95, CHCl3)Source of chirality: the precursorAbsolute configuration: (R,R,R)