Reaktion #64785

Reaktionsgleichung

Bis(trimethylsilyl)trifluoroacetamide

L-isoleucine

2-trifluoromethyl-3-acetylthiopropionyl chloride

water

bis(trimethylsilyl)trifluoroacetamide

→

(S)-N-[2-[(acetylthio)methyl]-3,3,3-trifluoro-1-oxopropyl]-L-isoleucine

Lösungsmittel

acetonitrile

acetonitrile

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.DISSOLUTIONAt this time approximately one third of the solid had dissolved
2. 2
   workup.STIRRINGthe mixture was stirred for 45 minutes
3. 3
   TemperaturThe mixture was cooled to 0° C.
4. 4
   workup.STIRRINGAfter stirring for 18 hours at room temperature
5. 5
   Extraktionthe resulting mixture was extracted with ethyl acetate (2×150 mL)
6. 6
   WaschenThe combined organic layers were washed with brine (100 mL)
7. 7
   Trocknendried (MgSO4)
8. 8
   Einengenconcentrated
9. 9
   Sonstigeto afford an oily residue which
10. 10
    SonstigeAfter several chromatographies, triturations and recrystallizations 1.41 g
11. 11
    Sonstigem.p. 81°-85° C., [α]D =-105.5° (c=0.38, methanol) were isolated

Vorschrift

Bis(trimethylsilyl)trifluoroacetamide (16 mL, 60 mmol.) was added to a suspension of L-isoleucine (2.62 g., 20 mmol.) in 40 mL of acetonitrile at 0° C. The suspension was allowed to warm to room temperature and stirred for 2 hours. At this time approximately one third of the solid had dissolved. An additional amount of bis(trimethylsilyl)trifluoroacetamide (4 mL, 15 mmol.) was added and the mixture was stirred for 45 minutes. The mixture was cooled to 0° C. and 2-trifluoromethyl-3-acetylthiopropionyl chloride (4.7 g., 20 mmol.) was added dropwise over 15 minutes as a solution in 10 mL of acetonitrile. After stirring for 18 hours at room temperature, the reaction mixture was a clear light yellow solution. Approximately 150 mL of water was added and the resulting mixture was extracted with ethyl acetate (2×150 mL). The combined organic layers were washed with brine (100 mL), dried (MgSO4), and concentrated to afford an oily residue which was preadsorbed onto Celite for chromatography. After several chromatographies, triturations and recrystallizations 1.41 g. of (R)-N-[2-[(acetylthio)methyl]-3,3,3-trifluoro-1-oxopropyl]-L-isoleucine; m.p. 81°-85° C., [α]D =-105.5° (c=0.38, methanol) were isolated and 1.56 g. of (S)-N-[2-[(acetylthio)methyl]-3,3,3-trifluoro-1-oxopropyl]-L-isoleucine, m.p. 111°-112° C., [α]D =+122.6° (c=0.38, methanol) were isolated.

Quelle