Diisopropylamine → (1-(tert-Butoxycarbonyl)-4-fluoro-1H-indol-2-yl)boronic acid

HRID 595643ノート

反応式

HRID 595643 の反応式
C(NC(C)C)(C)C.[Li]CCCC.[F:13][C:14]1[CH:22]=[CH:21][CH:20]=[C:19]2[C:15]=1[CH:16]=[CH:17][N:18]2[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24].[B:30](OC(C)C)([O:35]C(C)C)[O:31]C(C)C>C1COCC1>[C:26]([O:25][C:23]([N:18]1[C:19]2[C:15](=[C:14]([F:13])[CH:22]=[CH:21][CH:20]=2)[CH:16]=[C:17]1[B:30]([OH:35])[OH:31])=[O:24])([CH3:29])([CH3:28])[CH3:27]

参加物

6

反応物 4

HCID 7912DiisopropylamineHCID 21531Triisopropyl borateHCID 14710388tert-Butyl 4-fluoro-1H-indole-1-carboxylateHCID 178418339Butyllithium

生成物 1

HCID 44118245(1-(tert-Butoxycarbonyl)-4-fluoro-1H-indol-2-yl)boronic acid収率 66.6%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

To a solution of diisopropylamine (175 mL, 1.25 mol) in THF (800 mL) at 0° C. was added n-BuLi (500 mL, 1.25 mol, 2.5 M in hexane) dropwise. The mixture was stirred at 0° C. for 40 min. Then the mixture was cooled to −78° C. Tert-butyl 4-fluoro-1H-indole-1-carboxylate (118 g, 0.50 mol) in THF (300 mL) was added dropwise slowly, followed by triisopropyl borate (231 mL, 1.00 mol). The mixture was stirred at −78° C. for another 40 min. The reaction was monitored by HPLC. When the reaction was completed, the reaction was quenched with NH4Cl (sat. 500 mL). Then the mixture was adjusted to pH=6 with 1 N HCl. Extracted with EtOAc (2000 mL) and the combined organic layers were washed with brine (500 mL), dried over Na2SO4, filtered and concentrated. The obtained solid was recrystallized with EtOAc and PE to give (1-(tert-butoxycarbonyl)-4-fluoro-1H-indol-2-yl)boronic acid (93 g, yield: 64%, store in fridge). 1H-NMR (CDCl3, 400 MHz) δ 7.77 (d, J=8.4 Hz, 1H), 7.57 (s, 1H), 7.44 (s, 2H), 7.24 (m, 1H), 6.90 (m, 1H), 1.66 (s, 9H). MS (M+H)+: 280.

後処理

  1. temperatureThen the mixture was cooled to −78° C
  2. stirringThe mixture was stirred at −78° C. for another 40 min
  3. customthe reaction was quenched with NH4Cl (sat. 500 mL)
  4. extractionExtracted with EtOAc (2000 mL)
  5. washthe combined organic layers were washed with brine (500 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe obtained solid was recrystallized with EtOAc and PE

出典と根拠

ORDレコード
ord-0d3e4ec0930d4835a09e0ed69ae04822
出典データセット
uspto-grants-2016_01
特許番号
US09243002B2

反応ノート

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