반응 #64796

반응 방정식

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

용매

—

hexanes

methanol

acetic acid

acetonitrile

acetonitrile

반응 조건

후처리

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

실험 절차

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).

출처