Reaktion #47395

Reaktionsgleichung

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

Ausbeute 28.3%

Lösungsmittel

acetonitrile

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthe resulting mixture refluxed for 14 h
2. 2
   FiltrationThe mixture was filtered
3. 3
   Sonstigeto remove salts
4. 4
   Waschenthe filtrate washed successively with saturated ammonium chloride, water, and brine
5. 5
   TrocknenThe solution was dried over sodium sulfate
6. 6
   Filtrationfiltered
7. 7
   Sonstigeevaporated
8. 8
   workup.DISSOLUTIONThe residue was dissolved in tetrahydrofuran (10 mL)
9. 9
   Sonstigetransferred to an Emry Optimizer microwave reaction vessel
10. 10
    Temperaturheated at 160° C., for 4 h
11. 11
    SonstigeThe crude product obtained after aqueous work-up
12. 12
    Sonstigewas purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 100 g, 5% to 60% ethyl acetate/hexanes)

Vorschrift

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.

Quelle