تفاعل #47671

ord-c340630b5e7a4d41953dd76d267699a5

المذيبات

ظروف التفاعل

درجة الحرارة
100°CELSIUS
الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

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

الإجراء التجريبي

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.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US07741327B2uspto-grants-2010_06