Реакция #47671

Уравнение реакции

ethyl acetate

(L)-leucine methyl ester hydrochloride

(E)-4-bromo-3-(2-methyl-benzooxazol-4-yloxy)-but-2-enoic acid ethyl ester

N,N-diisopropylethylamine

→

(S)-4-methyl-2-[4-(2-methyl-benzooxazol-4-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid methyl ester

Выход 56.0%

Растворители

acetonitrile

Условия реакции

Обработка

1. 1
   ТемператураThe reaction mixture was then cooled to room temperature
2. 2
   ФильтрацияThe mixture was then filtered
3. 3
   ПромывкаThe filtrate was washed successively with aqueous saturated ammonium chloride, water, and brine
4. 4
   Сушкаdried over sodium sulfate
5. 5
   Фильтрацияfiltered
6. 6
   Концентрированиеconcentrated in vacuo
7. 7
   workup.DISSOLUTIONThe residue was dissolved in tetrahydrofuran (5 mL)
8. 8
   Другоеmicrowaved in an Emry Optimizer microwave reaction vessel at 160° C., for 3 h
9. 9
   ТемператураThe mixture was then cooled
10. 10
    Концентрированиеconcentrated in vacuo
11. 11
    Другоеthe residue was purified by ISCO Combiflash chromatography (40 g Silicycle, 5% to 50% ethyl acetate/hexanes)

Методика

A mixture of (L)-leucine methyl ester hydrochloride (0.570 g, 3.14 mmol), (E)-4-bromo-3-(2-methyl-benzooxazol-4-yloxy)-but-2-enoic acid ethyl ester (0.970 g, 2.85 mmol) and N,N-diisopropylethylamine (0.809 g, 6.21 mmol) in acetonitrile (20 mL) in a sealed tube was heated at 100° C. for 5 h. The reaction mixture was then cooled to room temperature and ethyl acetate was added. The mixture was then filtered. The filtrate was washed successively with aqueous saturated ammonium chloride, water, and brine and then dried over sodium sulfate, filtered and concentrated in vacuo. The residue was dissolved in tetrahydrofuran (5 mL) and microwaved in an Emry Optimizer microwave reaction vessel at 160° C., for 3 h. The mixture was then cooled and concentrated in vacuo and the residue was purified by ISCO Combiflash chromatography (40 g Silicycle, 5% to 50% ethyl acetate/hexanes) to afford (S)-4-methyl-2-[4-(2-methyl-benzooxazol-4-yloxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-pentanoic acid methyl ester (0.570 g, 56%) as a brown oil.

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