Toluene → 4'-(4-Cyclopropyl-2-ethoxy-5-formylimidazol-1-ylmethyl)-3'-fluoro-biphenyl-2-carboxylic acid t-butyl ester

HRID 1517743ノート

反応式

HRID 1517743 の反応式
[C:1]([O:5][C:6]([C:8]1[C:9]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20][N:21]3[C:25]([CH:26]=[O:27])=[C:24](Br)[N:23]=[C:22]3[O:29][CH2:30][CH3:31])=[C:16]([F:32])[CH:15]=2)=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:33]1(B(O)O)[CH2:35][CH2:34]1.C1(C)C=CC=CC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(=O)([O-])[O-].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[C:1]([O:5][C:6]([C:8]1[C:9]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20][N:21]3[C:25]([CH:26]=[O:27])=[C:24]([CH:33]4[CH2:35][CH2:34]4)[N:23]=[C:22]3[O:29][CH2:30][CH3:31])=[C:16]([F:32])[CH:15]=2)=[CH:10][CH:11]=[CH:12][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

8

反応物 5

HCID 1140Toluene2 回HCID 11430Potassium CarbonateHCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 510415724'-(4-Bromo-2-ethoxy-5-formylimidazol-1-ylmethyl)-3'-fluorobiphenyl-2-carboxylic acid t-butyl ester

生成物 1

HCID 592839094'-(4-Cyclopropyl-2-ethoxy-5-formylimidazol-1-ylmethyl)-3'-fluoro-biphenyl-2-carboxylic acid t-butyl ester収率 49.3%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒2 回

実験手順

4′-(4-Bromo-2-ethoxy-5-formylimidazol-1-ylmethyl)-3′-fluorobiphenyl-2-carboxylic acid t-butyl ester (2.6 g, 5.24 mmol), cyclopropylboronic acid (900 mg, 10.5 mmol) 1.0 M tricyclohexylphosphine in toluene (524 μL, 524 μmol), potassium phosphate (3.9 g, 18.4 mmol), and palladium acetate (118 mg, 524 μmol) were combined and dissolved in toluene (95.0 mL, 892 mmol). The mixture was stirred at room temperature under nitrogen for 20 minutes. Water (5.1 mL, 183 mmol) and potassium carbonate (2.5 g, 18.4 mmol) were then added and the mixture heated at 100° C. for 3 hours. Water (100 mL) was added and the layers separated. The organics were washed with water (50 mL) and saturated aqueous NaCl (50 mL), dried over Na2SO4, and the solvent evaporated. The product was purified by flash chromatography (0-40% EtOAc in hexanes to yield compound A (1.2 g).

後処理

  1. temperaturethe mixture heated at 100° C. for 3 hours
  2. customthe layers separated
  3. washThe organics were washed with water (50 mL) and saturated aqueous NaCl (50 mL)
  4. dry with materialdried over Na2SO4
  5. customthe solvent evaporated
  6. customThe product was purified by flash chromatography (0-40% EtOAc in hexanes

出典と根拠

ORDレコード
ord-5014c378b349435d91a67d429f65c0ae
出典データセット
uspto-grants-2012_07
特許番号
US08232306B2

反応ノート

読み込み中…