Oxazole → Methyl 3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate

HRID 14072

반응식

HRID 14072 반응식
[O:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C([Li])CCC.[CH2:11]([N:14]([CH2:28][CH2:29][CH3:30])[C:15]([C:17]1[CH:18]=[C:19]([CH:24]=[C:25](I)[CH:26]=1)[C:20]([O:22][CH3:23])=[O:21])=[O:16])[CH2:12][CH3:13]>O1CCCC1.C(OCC)(=O)C.[Cl-].[Zn+2].[Cl-]>[CH2:28]([N:14]([CH2:11][CH2:12][CH3:13])[C:15]([C:17]1[CH:18]=[C:19]([CH:24]=[C:25]([C:2]2[O:1][CH:5]=[CH:4][N:3]=2)[CH:26]=1)[C:20]([O:22][CH3:23])=[O:21])=[O:16])[CH2:29][CH3:30]

참가 물질

7

반응물 3

HCID 9255OxazoleHCID 21086179Methyl 3-[(dipropylamino)carbonyl]-5-iodobenzoateHCID 178418339Butyllithium

생성물 1

HCID 21939658Methyl 3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate

시약·촉매·용매 3

HCID 3007855Zincchloride촉매HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

반응 조건

온도
0 °C

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).

후처리

  1. customwithout further purification
  2. customin the following reaction
  3. temperatureThe reaction mixture is heated
  4. temperatureat reflux for 3 h
  5. temperatureThe reaction mixture is cooled
  6. filtrationfiltered
  7. washwashed with saturated sodium bicarbonate, water, and brine
  8. dry with materialdried (sodium sulfate)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customPurification by flash column chromatography (silica gel, 60% ethyl acetate/hexane)

출처 및 근거

ORD 기록
ord-13f72cbfbaea442d8cdb7ad596d52041
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07727997B2

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