반응 #42344

ord-d945e176239c4c6c9e6013b66b49819e

반응 조건

온도
0°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도The reaction mixture is heated
  2. 2
    온도at reflux for 2 h
  3. 3
    온도The reaction mixture is cooled
  4. 4
    세척washed with water, and brine
  5. 5
    건조dried (sodium sulfate)
  6. 6
    여과filtered
  7. 7
    농축concentrated under reduced pressure
  8. 8
    기타Purification by flash column chromatography (silica gel, 60% ethyl acetate/hexane)
  9. 9
    기타provides a solid
  10. 10
    workup.ADDITIONis added
  11. 11
    세척washed with 1N hydrochloric acid (aq), water, and brine
  12. 12
    건조dried (sodium sulfate)
  13. 13
    여과filtered
  14. 14
    농축concentrated under reduced pressure

실험 절차

To a −70° C. stirred solution of oxazole (330 mg, 4.8 mmol) in tetrahydrofuran (4 mL) is added n-butyllithium (1.6 M in hexanes, 3.3 mL, 5.3 mmol). After 30 min, zinc chloride (1 M in diethyl ether, 14.5 mL, 14.5 mmol) is added and the reaction mixture is warmed to 0° C. for 1 h. To this mixture is added a solution of methyl 3-iodo-5-{[methyl(propyl)amino]carbonyl}benzoate (1.6 g, 4.5 mmol) in anhydrous tetrahydrofuran (3 mL) followed by palladium(0)tetrakis(triphenylphosphine) (221 mg, 0.19 mmol). The reaction mixture is heated at reflux for 2 h. The reaction mixture is cooled, diluted with ethyl acetate, washed with water, and brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica gel, 60% ethyl acetate/hexane) provides a solid. The solid is redissolved in 1:1:1 tetrahydrofuran/methanol/water (9 mL), and lithium hydroxide monohydrate (311 mg, 7.4 mmol) is added and stirred 2 h at room temperature. The reaction is diluted in chloroform and washed with 1N hydrochloric acid (aq), water, and brine, dried (sodium sulfate), filtered and concentrated under reduced pressure to give the title compound. ESI MS m/z 287.3 [M−H]−.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US07727997B2uspto-grants-2010_06