Reaktion #61124

Reaktionsgleichung

sodium borohydride

(2S,3S)-N-(4-Acetyl-thiazol-2-yl)-2-[(R)-4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2,5-dioxo-imidazolidin-1-yl]-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide

methanol

potassium hydrogen phosphate

sodium borohydride

→

(2S,3S)-2-[(R)-4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2,5-dioxo-imidazolidin-1-yl]-N-[4-(1-hydroxy-propyl)-thiazol-2-yl]-3-phenyl-butyramide

Ausbeute 73.0%

Lösungsmittel

brine

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction mixture was then cooled in an ice bath
2. 2
   workup.STIRRINGstirring
3. 3
   workup.WAITcontinued for 1 hour
4. 4
   workup.STIRRINGthe cloudy mixture was stirred for a few minutes
5. 5
   Extraktionextracted with ethyl acetate (3×25 mL)
6. 6
   WaschenThe combined organic extracts were washed with saturated brine
7. 7
   Trocknendried over sodium sulfate
8. 8
   Einengenconcentrated in vacuo
9. 9
   workup.ADDITIONthen treated with diethyl ether (2 mL)
10. 10
    Sonstigethis turbid solution was further precipitated with of hexanes (3 mL)
11. 11
    workup.STIRRINGThe mixture was stirred for 5 minutes
12. 12
    Filtrationthen filtered over a 1.7 cm funnel
13. 13
    Waschenwashed with hexanes and air
14. 14
    Sonstigedried

Vorschrift

(2S,3S)-N-(4-Acetyl-thiazol-2-yl)-2-[(R)-4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2,5-dioxo-imidazolidin-1-yl]-3-phenyl-N-(4-propionyl-thiazol-2-yl)-butyramide (from example 5a) (20 mg, 0.037 mmol) was dissolved in warm dry methanol (5 mL). The reaction mixture was then cooled in an ice bath and sodium borohydride (1.56 mg, 0.041 mmol) was added. The reaction was stirred at 5° C. for 30 minutes, additional sodium borohydride (1.56 mg, 0.041 mmol) was added and stirring continued for 1 hour. The clear solution was treated with 1.5 N aqueous potassium hydrogen phosphate (1 mL) and the cloudy mixture was stirred for a few minutes, then diluted with saturated brine and extracted with ethyl acetate (3×25 mL). The combined organic extracts were washed with saturated brine, dried over sodium sulfate and concentrated in vacuo. The pale yellow residue was taken into a small amount of dichloromethane (0.5 ml) then treated with diethyl ether (2 mL) and this turbid solution was further precipitated with of hexanes (3 mL). The mixture was stirred for 5 minutes then filtered over a 1.7 cm funnel, washed with hexanes and air dried to give (2S,3S)-2-[(R)-4-(2,3-dihydro-benzo[1,4]dioxin-6-yl)-2,5-dioxo-imidazolidin-1-yl]-N-[4-(1-hydroxy-propyl)-thiazol-2-yl]-3-phenyl-butyramide as a white solid (14.5 mg, 73%).

Quelle