Reaction #47671

Reaction equation

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

Yield 56.0%

Solvents

acetonitrile

Conditions

Workup

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

Procedure

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.

Source