Reacción #47671

Ecuación de reacción

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

Rendimiento 56.0%

Disolventes

acetonitrile

Condiciones de reacción

Tratamiento posterior

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

Procedimiento

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.

Fuente