1-((1,1-Dimethylethyl)dimethylsilyl)-1H-imidazole → Methyl 3-[(dipropylamino)carbonyl]-5-(1H-imidazol-2-yl)benzoate

HRID 14062ノート

反応式

HRID 14062 の反応式
[Si]([N:8]1[CH:12]=[CH:11][N:10]=[CH:9]1)(C(C)(C)C)(C)C.C([Li])CCC.[CH2:18]([N:21]([CH2:35][CH2:36][CH3:37])[C:22]([C:24]1[CH:25]=[C:26]([CH:31]=[C:32](I)[CH:33]=1)[C:27]([O:29][CH3:30])=[O:28])=[O:23])[CH2:19][CH3:20]>O1CCCC1.C(OCC)(=O)C.[Cl-].[Zn+2].[Cl-]>[CH2:35]([N:21]([CH2:18][CH2:19][CH3:20])[C:22]([C:24]1[CH:25]=[C:26]([CH:31]=[C:32]([C:9]2[NH:8][CH:12]=[CH:11][N:10]=2)[CH:33]=1)[C:27]([O:29][CH3:30])=[O:28])=[O:23])[CH2:36][CH3:37]

参加物

7

反応物 3

HCID 1713851-((1,1-Dimethylethyl)dimethylsilyl)-1H-imidazoleHCID 21086179Methyl 3-[(dipropylamino)carbonyl]-5-iodobenzoateHCID 178418339Butyllithium

生成物 1

HCID 21086171Methyl 3-[(dipropylamino)carbonyl]-5-(1H-imidazol-2-yl)benzoate

試薬・触媒・溶媒 3

HCID 3007855Zincchloride触媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

To a −70° C. stirred solution of 1-tert-butyldimethylsilylimidazole (602 mg, 3.3 mmol) in tetrahydrofuran (10 mL) is added n-butyllithium (1.6 M in hexanes, 2.3 mL, 3.63 mmol). After 30 min, zinc chloride (1 M in diethyl ether, 9.9 mL, 9.9 mmol) is added and the reaction mixture is warmed to 0° C. for 1 h. To this mixture is then added methyl 3-[(dipropylamino)carbonyl]-5-iodobenzoate prepared by the method in Example SP-281, step 2 (1.17 g, 3 mmol) followed by palladium(0)tetrakis(triphenylphosphine) (173 mg, 0.15 mmol). The reaction mixture is heated at reflux for 15 h. The reaction mixture is diluted with ethyl acetate (50 mL), washed with water, and brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica gel, 1-5% methanol/methylene chloride) provides the title compound in pure form. 1H NMR (300 MHz, CDCl3) δ 8.64 (s, 1H), 8.14 (s, 1H), 7.97 (s, 1H), 7.19 (s, 2H), 3.96 (s, 3H), 3.51 (m, 2H), 3.32 (m, 2H), 1.73 (m, 2H), 1.57 (m, 2H), 1.01 (m, 3H), 0.73 (m, 3H).

後処理

  1. temperatureThe reaction mixture is heated
  2. temperatureat reflux for 15 h
  3. washwashed with water, and brine
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification by flash column chromatography (silica gel, 1-5% methanol/methylene chloride)

出典と根拠

ORDレコード
ord-b6666355a0f3409d9b305dcb26d75071
出典データセット
uspto-grants-2010_06
特許番号
US07727997B2

反応ノート

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