Reaktion #307918

Reaktionsgleichung

sodium hydroxide

(S)-2-acetylamino-4,5,6,7-tetrahydro-benzothiazole-6-carboxylic acid

triethylamine

isopropanol

diphenylphosphoryl azide

→

isopropyl(S)-(2-acetylamino-4,5,6,7-tetrahydro-benzothiazol-6-yl)-carbamate

Lösungsmittel

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeA 2000 ml reactor equipped with mechanical stirrer
2. 2
   workup.ADDITIONis dropped
3. 3
   workup.WAITAfter 2 hours
4. 4
   Temperaturthe reaction mixture is cooled to 20-30° C.
5. 5
   workup.DISTILLATIONIsopropanol is distilled off under vacuum
6. 6
   workup.ADDITION400 ml of ethyl acetate are added
7. 7
   TemperaturThe mixture is refluxed for 15 minutes
8. 8
   Filtrationthe hot suspension is filtered through Celite
9. 9
   TemperaturThe solution is cooled to 20-30° C.
10. 10
    workup.ADDITIONadded with of 1800 ml of water
11. 11
    SonstigeThe phases are separated
12. 12
    Einengenthe organic phase concentrated to dryness
13. 13
    TemperaturThe suspension is heated at 50° C. for 1 hour
14. 14
    Temperaturcooled to 20° C.
15. 15
    Filtrationfiltered

Vorschrift

A 2000 ml reactor equipped with mechanical stirrer, thermometer and condenser are loaded with 100 g of (S)-2-acetylamino-4,5,6,7-tetrahydro-benzothiazole-6-carboxylic acid [(I), R=—NH—CO—CH3] of 97% enantiomeric purity, suspended in 700 ml of isopropanol; 84.16 g of triethylamine are added. The mixture is refluxed (about 80° C.) and a solution consisting of 120.42 g of diphenylphosphoryl azide (DPPA) is dropped therein in 2 hours. After 2 hours, the reaction mixture is cooled to 20-30° C. and added with 500 ml of water and 1.6 g of sodium hydroxide. Isopropanol is distilled off under vacuum, then 400 ml of ethyl acetate are added. The mixture is refluxed for 15 minutes, then the hot suspension is filtered through Celite. The solution is cooled to 20-30° C. and added with of 1800 ml of water. The phases are separated and the organic phase concentrated to dryness. The residue is taken up with 200 ml of acetonitrile. The suspension is heated at 50° C. for 1 hour, then cooled to 20° C. and filtered to obtain 75 g of isopropyl(S)-(2-acetylamino-4,5,6,7-tetrahydro-benzothiazol-6-yl)-carbamate, with 97% enantiomeric purity.

Quelle