Water → HCID 178488146, Verbindung

Beteiligte Stoffe

Reaktionsschritte

1.2 g (3.6 mmol) of 2-{[(4-chloro-3,5-dimethyl-2-pyridinyl)methyl]thio}-5-methoxy-1H-benzimidazole was mixed with toluene (40 mL). The mixture was concentrated until half the volume was left. Water (38 mg, 2.1 mmol), (S,S)-diethyl tartrate (1.85 g, 9.0 mmol) and titanium tetraisopropoxide (1.0 g, 3.6 mmol) were added in the given order while stirring. The mixture was then stirred at 50° C. for an hour and then N,N-diisopropylethylamine (0.46 g, 3.6 mmol) was added at room temperature. After 15 minutes cumene hydroperoxide (80% in cumene, 0.69 g, 3.6 mmol) was added dropwise and stirring was then continued for 2 h at room temperature. The optical purity of crude sulfoxide turned out to be 75% ee as determined by chiral HPLC analysis of the solution. The mixture was washed with water and then evaporated. The product was purified by chromatography on silica gel using methanol/dichloromethane as eluent (gradient, 1-7% MeOH) and this afforded 1.0 g of a crude product as a solid. Recrystallisation from hot acetonitrile gave 0.35 g of a white solid with an enantiomeric excess of 51%. Next, the mother liqueur from the filtration was concentrated and this material was then also recrystallised from acetonitrile to give 0.35 g of the title compound as a crystalline product with an enantiomeric excess of 92.5%.

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