반응 #42350

ord-13f72cbfbaea442d8cdb7ad596d52041

반응 방정식

[Li][CH2]CCC
n-butyllithium
c1cocn1
oxazole
CCCN(CCC)C(=O)c1cc(I)cc(C(=O)OC)c1
methyl 3-[(dipropylamino)carbonyl]-5-iodobenzoate
CCCN(CCC)C(=O)c1cc(C(=O)OC)cc(-c2ncco2)c1
title compound
CCCN(CCC)C(=O)c1cc(C(=O)OC)cc(-c2ncco2)c1
Methyl 3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate

반응 조건

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

후처리

  1. 1
    기타without further purification
  2. 2
    기타in the following reaction
  3. 3
    온도The reaction mixture is heated
  4. 4
    온도at reflux for 3 h
  5. 5
    온도The reaction mixture is cooled
  6. 6
    여과filtered
  7. 7
    세척washed with saturated sodium bicarbonate, water, and brine
  8. 8
    건조dried (sodium sulfate)
  9. 9
    여과filtered
  10. 10
    농축concentrated under reduced pressure
  11. 11
    기타Purification by flash column chromatography (silica gel, 60% ethyl acetate/hexane)

실험 절차

3-[(Dipropylamino)carbonyl]-5-iodobenzoic acid (12 g, 32 mmol) is dissolved in 20% methanol/benzene (480 mL), and 2M trimethylsilyldiazomethane in hexane (19 mL, 38 mmol) is added slowly. Upon completion of the addition, the solution is concentrated under reduced pressure to give methyl 3-[(dipropylamino)carbonyl]-5-iodobenzoate for use without further purification in the following reaction. To a −70° C. stirred solution of oxazole (120 mg, 1.7 mmol) in tetrahydrofuran (4 mL) is added n-butyllithium (1.6 M in hexanes, 1.2 mL, 1.9 mmol). After 30 min, zinc chloride (1 M in diethyl ether, 5.2 mL, 5.2 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-[(dipropylamino)carbonyl]-5-iodobenzoate (643 mg, 1.6 mmol) in anhydrous tetrahydrofuran (3 mL) followed by palladium(0)tetrakis(triphenylphosphine) (80 mg, 0.07 mmol). The reaction mixture is heated at reflux for 3 h. The reaction mixture is cooled, diluted with ethyl acetate, filtered, washed with saturated sodium bicarbonate, water, and brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica gel, 60% ethyl acetate/hexane) provides the title compound in pure form. 1H NMR (400 MHz, CDCl3) δ 8.77 (s, 1H), 8.27 (s, 1H), 8.14 (s, 1H), 7.80 (s, 1H) 7.32 (s, 1H), 3.52 (t, 2H), 3.22 (t, 2H), 1.75 (m, 2H), 1.30 (m, 2H), 0.97 (t, 3H), 0.79 (t, 3H).

출처

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