Reaktion #64777

Reaktionsgleichung

ethyl acetate

2-Trifluoromethyl-3-acetylthio propionyl chloride

L-phenylalanine

bis(trimethylsilyl)trifluoroacetamide

→

N-[2-[(Acetylthio)methyl]-3,3,3-trifluoro-1-oxopropyl]-L-phenylalanine

Lösungsmittel

—

hexanes

methanol

acetic acid

acetonitrile

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturslowly warm to room temperature
2. 2
   workup.ADDITIONwas added dropwise over a period of about 45 minutes at 5° C.
3. 3
   Temperaturto warm to room temperature
4. 4
   workup.STIRRINGstir overnight
5. 5
   SonstigeThe mixture was evaporated under reduced pressure
6. 6
   Sonstigeto give a light yellow oil
7. 7
   SonstigeThe oil was partitioned between water (75 mL) and ethyl acetate (100 mL)
8. 8
   FiltrationThe entire mixture was filtered
9. 9
   Sonstigeto remove a white precipitate (phenylalanine)
10. 10
    Sonstigethe organic layer was separated
11. 11
    ExtraktionThe aqueous phase was extracted once more with 50 mL of ethyl acetate
12. 12
    ExtraktionThe combined ethyl acetate extract
13. 13
    Waschenwas washed with brine
14. 14
    Trocknendried over anhydrous magnesium sulfate
15. 15
    Sonstigeevaporated
16. 16
    Sonstigeto give 20.1 g of the crude mixture of diastereomers as a light yellow solid
17. 17
    Sonstigechromatographed on silica gel (125:1 silica gel to compound)
18. 18
    Sonstigehexanes:acetic acid, 100:100:1 as the eluent, to yield 0.370 g of the
19. 19
    Waschenfaster eluting diastereomer (isomer A) and 0.383 g of the
20. 20
    Waschenslower eluting diastereomer (isomer B)
21. 21
    Sonstigechromatographed similarly
22. 22
    Sonstigeto yield 2.67 g of isomer A and 2.92 g of isomer B

Vorschrift

A stirred suspension of L-phenylalanine (7.60 g, 46 mmol) in 45 mL of dry acetonitrile under argon was cooled to 0° C. and bis(trimethylsilyl)trifluoroacetamide (24.7 mL, 92 mmol) was added. The reaction mixture was allowed to stir and slowly warm to room temperature. After 4 hours, practically all of the amino acid was in the solution, which was light yellow in color. 2-Trifluoromethyl-3-acetylthio propionyl chloride (4.69 g, 20 mmol), dissolved in 10 mL of acetonitrile, was added dropwise over a period of about 45 minutes at 5° C. and thereafter the reaction mixture was allowed to warm to room temperature and stir overnight. The mixture was evaporated under reduced pressure to give a light yellow oil. The oil was partitioned between water (75 mL) and ethyl acetate (100 mL). The entire mixture was filtered to remove a white precipitate (phenylalanine), and the organic layer was separated. The aqueous phase was extracted once more with 50 mL of ethyl acetate. The combined ethyl acetate extract was washed with brine, dried over anhydrous magnesium sulfate and evaporated to give 20.1 g of the crude mixture of diastereomers as a light yellow solid. A 2.0 g portion of the product was flash chromatographed on silica gel (125:1 silica gel to compound), using ethyl acetate: hexanes:acetic acid, 100:100:1 as the eluent, to yield 0.370 g of the faster eluting diastereomer (isomer A) and 0.383 g of the slower eluting diastereomer (isomer B). The remaining 18.1 g of crude material was flash chromatographed similarly to yield 2.67 g of isomer A and 2.92 g of isomer B. The combined yield of isomer A was 3.04 g as a white crystalline solid, m.p. 183°-185° C., TLC Rf =0.30 (200:100:1 ethyl acetate:hexanes:acetic acid), [α]D =-98.8° (c=1.00, methanol).

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