Reaktion #305631

Reaktionsgleichung

2-[[3-methyl-4-nitro-2-piridyl]methylthio]benzimidazole

(+)-diethyl-L-tartrate

diisopropylethylamine

cumene hydroperoxide

cumene hydroperoxide

sodium thiosulphate

sodium bisulfite

sodium hydroxide

isopropyl acetate

→

(R)-2-[[[3-methyl-4-nitro-2-piridyl]-methyl]sulfinyl]benzimidazole

Ausbeute 80.0%

Lösungsmittel

THF

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturto reflux temperature
2. 2
   Temperaturmaintained
3. 3
   Temperaturthe mixture is maintained
4. 4
   workup.STIRRINGunder stirring
5. 5
   Temperaturat reflux temperature till the formation of a clear solution
6. 6
   TemperaturThe solution is then cooled
7. 7
   Sonstigethe range temperature between −5° C. and 0° C.
8. 8
   workup.ADDITIONthe solution is treated
9. 9
   TemperaturThe reaction mixture is maintained
10. 10
    workup.STIRRINGunder stirring for 3 hours at about 0° C.
11. 11
    SonstigeAfter the separation of the phases the aqueous phase
12. 12
    Waschenis washed with toluene
13. 13
    Einengenconcentrated under reduced pressure
14. 14
    SonstigeThe oily residue so obtained
15. 15
    SonstigeThe so obtained mixture
16. 16
    FiltrationThe precipitated solid is then filtered off
17. 17
    Waschenwashed with isopropyl acetate and copious water
18. 18
    Sonstige9.2 g of product are recovered with a yield of 80%

Vorschrift

A mixture of 2-[[3-methyl-4-nitro-2-piridyl]methylthio]benzimidazole (10 g, 33 mmoles, containing 70 mg of water) and (+)-diethyl-L-tartrate (3.02 g, 14.6 mmoles), in THF (100 ml) is brought to reflux temperature and maintained under stirring for 30 minutes. Titanium isopropoxide (1.89 g, 6.66 mmoles) is added and the mixture is maintained under stirring at reflux temperature till the formation of a clear solution is achieved. The solution is then cooled and added with diisopropylethylamine (1.42 g, 10.9 mmoles). After having achieved the range temperature between −5° C. and 0° C., the solution is treated by slow cooling with cumene hydroperoxide 88% (17.3 g, 100 mmoles). The reaction mixture is maintained under stirring for 3 hours at about 0° C., then treated with a 30% sodium thiosulphate solution to decompose the residue of cumene hydroperoxide. After the separation of the phases the aqueous phase is washed with toluene, and the gathered up organic phases and concentrated under reduced pressure. The oily residue so obtained is taken up with water and treated with sodium hydroxide 30% till pH 12. The so obtained mixture is treated with isopropyl acetate and a solution of sodium bisulfite 25% till pH 9 is added. The precipitated solid is then filtered off and washed with isopropyl acetate and copious water. 9.2 g of product are recovered with a yield of 80% and a chemical and stereochemical purity (determined by HPLC and chiral HPLC) equal to or higher than 98%.

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