反応 #47395

反応方程式

ethyl acetate

(E)-4-bromo-3-(3-ethoxy-2,6-difluoro-phenoxy)-but-2-enoic acid ethyl ester

N,N-diisopropylethylamine

(L)-leucine methyl ester hydrochloride

→

(S)-2-[4-(3ethoxy-2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid methyl ester

収率 28.3%

溶媒

acetonitrile

acetonitrile

反応条件

後処理

1. 1
   温度the resulting mixture refluxed for 14 h
2. 2
   ろ過The mixture was filtered
3. 3
   その他to remove salts
4. 4
   洗浄the filtrate washed successively with saturated ammonium chloride, water, and brine
5. 5
   乾燥The solution was dried over sodium sulfate
6. 6
   ろ過filtered
7. 7
   その他evaporated
8. 8
   workup.DISSOLUTIONThe residue was dissolved in tetrahydrofuran (10 mL)
9. 9
   その他transferred to an Emry Optimizer microwave reaction vessel
10. 10
    温度heated at 160° C., for 4 h
11. 11
    その他The crude product obtained after aqueous work-up
12. 12
    その他was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 100 g, 5% to 60% ethyl acetate/hexanes)

実験手順

To a solution of (L)-leucine methyl ester hydrochloride (6.00 g, 0.033 mol) dissolved in acetonitrile (50 mL) was added (E)-4-bromo-3-(3-ethoxy-2,6-difluoro-phenoxy)-but-2-enoic acid ethyl ester (6.05 g) in acetonitrile (10 mL) and N,N-diisopropylethylamine (7.27 g, 0.056 mol) and the resulting mixture refluxed for 14 h. The reaction mixture was cooled to room temperature and then poured into ethyl acetate. The mixture was filtered to remove salts and the filtrate washed successively with saturated ammonium chloride, water, and brine. The solution was dried over sodium sulfate, filtered and evaporated. The residue was dissolved in tetrahydrofuran (10 mL) and then transferred to an Emry Optimizer microwave reaction vessel and heated at 160° C., for 4 h. The crude product obtained after aqueous work-up, was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 100 g, 5% to 60% ethyl acetate/hexanes) to afford (S)-2-[4-(3ethoxy-2,6-difluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid methyl ester (1.80 g, 28%) as an oil.

出典