반응 #64781

반응 방정식

bis(trimethylsilyl)trifluoroacetamide

ethyl acetate

2-trifluoromethyl-3-acetylthiopropionyl chloride

bis(trimethylsilyl)trifluoroacetamide

L-leucine

→

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

용매

methanol

acetic acid

hexane

acetonitrile

acetonitrile

반응 조건

후처리

1. 1
   온도was cooled to 0°-5° C.
2. 2
   기타resulted in a clear lemon color solution
3. 3
   workup.STIRRINGon additional stirring for one hour at room temperature
4. 4
   온도The reaction mixture was cooled to 0°-5° C.
5. 5
   workup.ADDITIONwas added dropwise over 45 minutes
6. 6
   workup.STIRRINGAfter stirring for 1.5 hours at 0°-5° C. to room temperature
7. 7
   기타completion of the reaction
8. 8
   기타The reaction mixture was evaporated under reduced pressure
9. 9
   기타to give a yellow oily residue which
10. 10
    기타was partitioned between ethyl acetate (75 mL) and water (50 mL)
11. 11
    추출The aqueous phase was further extracted with ethyl acetate (4×50 mL)
12. 12
    세척the combined extracts were washed with 75 mL of brine
13. 13
    건조dried (MgSO4)
14. 14
    기타evaporated
15. 15
    기타to give 10.3 g
16. 16
    기타chromatographed on 75 g
17. 17
    기타of silica gel eluting with ethyl acetate: hexanes:acetic acid, 100:100:1 to yield 0.15 g
18. 18
    세척of the faster eluting diastereomer (isomer A) and 0.12 g
19. 19
    세척of slower eluting diastereomer (isomer B)
20. 20
    기타chromatographed similarly (silica gel, 1300 g.) which
21. 21
    기타gave 2.5 g
22. 22
    workup.ADDITIONof a mixture of both the diastereomers, and 1.5 g
23. 23
    기타The mixed fractions were rechromatographed
24. 24
    기타to give 0.5 g
25. 25
    기타triturated with hexanes containing a few drops of ethyl acetate
26. 26
    여과filtered
27. 27
    기타dried
28. 28
    기타to yield 2.57 g

실험 절차

A stirred suspension of L-leucine (2.62 g., 20 mmol) in 35 mL of dry acetonitrile under argon was cooled to 0°-5° C. and bis(trimethylsilyl)trifluoroacetamide (10.62 mL, 40 mmol) was added. The reaction mixture was allowed to stir while slowly warming to room temperature. After 2 hours, another 3.5 mL (13 mmol) of bis(trimethylsilyl)trifluoroacetamide was added which resulted in a clear lemon color solution on additional stirring for one hour at room temperature. The reaction mixture was cooled to 0°-5° C. and 2-trifluoromethyl-3-acetylthiopropionyl chloride (4.69 g., 20 mmol.) dissolved in 8 mL of acetonitrile was added dropwise over 45 minutes. After stirring for 1.5 hours at 0°-5° C. to room temperature, TLC shows completion of the reaction. The reaction mixture was evaporated under reduced pressure to give a yellow oily residue which was partitioned between ethyl acetate (75 mL) and water (50 mL). The aqueous phase was further extracted with ethyl acetate (4×50 mL), the combined extracts were washed with 75 mL of brine, dried (MgSO4), and evaporated to give 10.3 g. of a yellow semi-solid residue. A 0.68 g. portion of this crude material was flash chromatographed on 75 g. of silica gel eluting with ethyl acetate: hexanes:acetic acid, 100:100:1 to yield 0.15 g. of the faster eluting diastereomer (isomer A) and 0.12 g. of slower eluting diastereomer (isomer B). The remaining 9.6 g. of crude material was flash chromatographed similarly (silica gel, 1300 g.) which gave 2.5 g. of isomer A, 2.7 g. of a mixture of both the diastereomers, and 1.5 g. of isomer B. The mixed fractions were rechromatographed using the same conditions to give 0.5 g. of isomer A and 1.25 g. of isomer B. Both the 2.5 g. and 0.5 g. portions of isomer A were combined, triturated with hexanes containing a few drops of ethyl acetate, filtered, and dried to yield 2.57 g. of the title isomer A product as a white crystalline solid, m.p. 150°-152° C., TLC Rf =0.40 (100:50:1 ethyl acetate:hexane:acetic acid), [α]D =-146.9° (c=1.00, methanol).

출처