반응 #611588

반응 방정식

N-Fluorobenzenesulfonimide

n-BuLi

2-{2-[tert-Butoxycarbonyl-(4-methoxy-benzyl)-amino]-thiazol-4-yl}-2-methyl-propionic acid ethyl ester

N,N-Diisopropyl amine

NH4Cl

→

compound

수율 24.0%

2-{2-[tert-Butoxycarbonyl-(4-methoxy-benzyl)-amino]-5-fluoro-thiazol-4-yl}-2-methyl-propionic acid ethyl ester

수율 24.0%

용매

THF

THF

THF

반응 조건

후처리

1. 1
   기타reaction mixture
2. 2
   workup.STIRRINGto stir for an additional 1 hr at −78° C
3. 3
   workup.ADDITIONwas added to reaction mixture dropwise
4. 4
   기타resulted
5. 5
   기타reaction mixture
6. 6
   기타Reaction mixture
7. 7
   추출was then extracted with (3×50 mL) ethyl acetate
8. 8
   세척organic layer was washed with brine
9. 9
   건조dried over anhydrous sodium sulfate
10. 10
    여과filtered
11. 11
    세척washed with ethyl acetate and solvent
12. 12
    기타was removed under reduced pressure
13. 13
    기타The crude material was purified by silica-gel column chromatography (4% ethyl acetate in hexane)

실험 절차

Under anhydrous condition n-BuLi (3.6 M solution in hexane, 2.55 mL, 9.20 mmol) was added to stirred solution of N,N-Diisopropyl amine (1.29 mL, 9.20 mmol) in 10 mL dry THF at −78° C. and reaction mixture was stirred for 1 hr. A solution of 2-{2-[tert-Butoxycarbonyl-(4-methoxy-benzyl)-amino]-thiazol-4-yl}-2-methyl-propionic acid ethyl ester (synthesized as per preparation 44; 2.0 g, 4.60 mmol) in 10 mL of dry THF was added dropwise to above reaction mixture and continued to stir for an additional 1 hr at −78° C. N-Fluorobenzenesulfonimide (2.17 g, 6.90 mmol) dissolved in 10 mL dry THF was added to reaction mixture dropwise and resulted reaction mixture was allowed to warm 0° C. within 3 hrs. Reaction mixture was poured on aq. saturated solution of NH4Cl (50 mL), mixture was then extracted with (3×50 mL) ethyl acetate; organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and washed with ethyl acetate and solvent was removed under reduced pressure. The crude material was purified by silica-gel column chromatography (4% ethyl acetate in hexane) to afford pure compound (0.5 g).

출처