Iodine → HCID 71061145、化合物

HRID 528961ノート

反応式

HRID 528961 の反応式
[C:1]([O:5][C:6]([C:8]1[CH:9]=[C:10]([CH:14]=[CH:15][CH:16]=1)[C:11]([OH:13])=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O)(=O)C.C(O)(=O)C.[I:25]C1C=CC=CC=1.II>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.ClCCCl>[C:1]([O:5][C:6]([C:8]1[CH:16]=[CH:15][C:14]([I:25])=[C:10]([CH:9]=1)[C:11]([OH:13])=[O:12])=[O:7])([CH3:4])([CH3:2])[CH3:3]

参加物

7

反応物 3

HCID 807IodineHCID 27609513-(tert-Butoxycarbonyl)benzoic acidHCID 12217721Iodo benzene diacetate

生成物 1

HCID 71061145HCID 71061145、化合物収率 62%

試薬・触媒・溶媒 3

HCID 67553Tetrabutylammonium Iodide触媒HCID 167845palladium(II) acetate触媒HCID 111,2-Dichloroethane溶媒

反応条件

温度
80 °C

実験手順

A 100 mL flask was charged with 3-(tert-butoxycarbonyl)benzoic acid (Matrix, 1.75 g, 7.87 mmol), palladium(II) acetate (0.177 g, 0.787 mmol), iodobenzene diacetate (2.54 g, 7.87 mmol), iodine (2.00 g, 7.87 mmol), and tetrabutylammonium iodide (2.91 g, 7.87 mmol). DCE (30 mL) was added and the dark reaction mixture was stirred at 80° C. for 6 h. The reaction mixture was concentrated in vacuo, diluted with 2M aq. sodium carbonate solution, and then extracted with ether (2×). The aqueous layer was made acidic with concentrated HCl and then extracted with EtOAc (2×). The pooled EtOAc extracts were dried over anhydrous magnesium sulfate and concentrated in vacuo to give crude 5-(tert-butoxycarbonyl)-2-iodobenzoic acid (1.7 g, 62%) which was used directly without further purification. A 200 mL round bottom flask was charged with crude 5-(tert-butoxycarbonyl)-2-iodobenzoic acid (1.7 g, 4.88 mmol) and HATU (2.23 g, 5.86 mmol). THF (30 mL), DMF (30.0 mL), and 2,6-lutidine (1.1 mL, 9.77 mmol) were added and the reaction mixture was stirred at room temperature for 1 h. Next, 1,2,3,4-tetrahydroisoquinoline (0.93 mL, 7.3 mmol) was then added. After stirring at room temperature 1 h, the reaction mixture was suspended in EtOAc, and then washed with sat. aq. sodium bicarbonate solution, 10% aq. LiCl solution, and then sat. aq. bicarbonate solution again. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography (Isco 120 g column eluting with 0-40% EtOAc/hexanes) to give the title compound (1.46 g, 65%) as a white foam. 1H NMR (CDCl3) δ 7.96-7.90 (m, 1H), 7.81-7.80 (m, 1H), 6.70-6.67 (m, 1H), 7.27-7.13 (m, 4H), 5.09-4.83 (m, 1H), 4.45-4.33 (m, 1H), 4.06-4.01 (m, 1H), 3.50-3.44 (m, 1H), 3.05-2.83 (m, 2H), 1.58 (s, 9H); MS(ESI+) m/z 464.1 (M+H)+.

後処理

  1. customthe dark reaction mixture
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. additiondiluted with 2M aq. sodium carbonate solution
  4. extractionextracted with ether (2×)
  5. extractionextracted with EtOAc (2×)
  6. dry with materialThe pooled EtOAc extracts were dried over anhydrous magnesium sulfate
  7. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-ef659e95b4824648ace3f344513a18b7
出典データセット
uspto-grants-2016_05
特許番号
US09346795B2

反応ノート

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