반응 #64797

반응 방정식

ethyl acetate

bis(trimethylsilyl)trifluoroacetamide

L-tryptophan

2-trifluoromethyl-3-acetylthiopropionyl chloride

→

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

용매

—

hexanes

methanol

acetic acid

acetonitrile

acetonitrile

반응 조건

후처리

1. 1
   온도was cooled to 0°-5° C.
2. 2
   온도the solution was cooled to 5° C.
3. 3
   workup.STIRRINGto stir overnight
4. 4
   온도gradually warming to room temperature
5. 5
   기타The solvent was evaporated
6. 6
   기타the yellow oily residue was partitioned between ethyl acetate (50 mL) and water (35 mL)
7. 7
   추출The aqueous phase was further extracted with ethyl acetate (3×50 mL)
8. 8
   추출the combined ethyl acetate extract
9. 9
   세척was washed with brine
10. 10
    건조dried (MgSO4)
11. 11
    기타evaporated to 14.15 g
12. 12
    기타chromatographed on silica gel (120:1 silica gel to compound)
13. 13
    기타hexanes:acetic acid, 150:100:1 to give 1.9 g
14. 14
    세척of the faster eluting diastereomer (isomer A), 4.2 g
15. 15
    세척of the slower eluting diastereomer (isomer B)
16. 16
    세척Further elution with ethyl acetate
17. 17
    기타hexanes:acetic acid, 200:100:1 gave an additional 170 mg
18. 18
    기타The mixed fractions were rechromatographed
19. 19
    기타to give 1.65 g
20. 20
    기타recrystallized from toluene
21. 21
    기타to give 2.8 g
22. 22
    기타of the crude product) was recrystallized from toluene
23. 23
    기타to give 260 mg

실험 절차

A stirred suspension of L-tryptophan (4.08 g., 20 mmol.) in 50 mL of dry acetonitrile under argon was cooled to 0°-5° C. and bis(trimethylsilyl)trifluoroacetamide (5.3 mL, 20 mmol.) was added. The reaction mixture was allowed to stir and warm to room temperature. After 3 hours, the solution was cooled to 5° C. and a solution of 2-trifluoromethyl-3-acetylthiopropionyl chloride (4.69 g., 20 mmol) in 7 mL of acetonitrile was gradually added over 45 minutes. The reaction mixture was allowed to stir overnight, gradually warming to room temperature. The solvent was evaporated and the yellow oily residue was partitioned between ethyl acetate (50 mL) and water (35 mL). The aqueous phase was further extracted with ethyl acetate (3×50 mL), and the combined ethyl acetate extract was washed with brine, dried (MgSO4) and evaporated to 14.15 g. of a yellow oily residue. A 12.25 g. portion of the product was flash chromatographed on silica gel (120:1 silica gel to compound) using ethyl acetate:hexanes:acetic acid, 150:100:1 to give 1.9 g. of the faster eluting diastereomer (isomer A), 4.2 g. of both diastereomers, and 1.5 g. of the slower eluting diastereomer (isomer B). Further elution with ethyl acetate:hexanes:acetic acid, 200:100:1 gave an additional 170 mg. of isomer B. The mixed fractions were rechromatographed using the same conditions to give 1.65 g. of isomer A and 1.76 g. of isomer B. The 1.9 g. and 1.65 g. portions of isomer A were combined and recrystallized from toluene to give 2.8 g. of off-white crystalline solid. An additional 360 mg. of isomer A (from flash chromatography of 1.5 g. of the crude product) was recrystallized from toluene to give 260 mg. of white crystalline solid; the total yield of title isomer A compound was 3.06 g.; m.p. 140°-143° C., TLC Rf =0.46 (300:100:1 ethyl acetate:hexanes:acetic acid), [α]D =-96.0° (c=1.00, methanol).

출처