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

HRID 1776941ノート

反応式

HRID 1776941 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.Cl>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

7

反応物 5

HCID 313Hydrochloric AcidHCID 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 76.7%

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 (7.5 mL, 0.11 mol) in THF (35 mL) at 0° C. was added n-BuLi (21 mL, 0.055 mol) dropwise. The mixture was stirred at 0° C. for 40 minutes. Then the mixture was cooled to −78° C. Tert-butyl 4-fluoro-1H-indole-1-carboxylate (5 g, 0.02 mol) in THF (13 mL) was added dropwise slowly. After addition, the mixture was stirred at −78° C. for 2 hours. Then triisopropyl borate (3.29 g, 0.03 mol) was added. The mixture was stirred at −78° C. for another 40 minutes. The reaction was monitored using TLC. When the reaction was completed, the mixture was adjusted to pH=6 with 1 N HCl. After extracted with EtOAc (25 mL×3), the combined organic layers were washed with brine (50 mL), dried over Na2SO4, filtered and concentrated in vacuo. The obtained solid was recrystallized with EtOAc and petroleum ether to provide (1-(tert-butoxycarbonyl)-4-fluoro-1H-indol-2-yl)boronic acid (4.5 g, yield: 76.7%, which might be unstable at high temp. work up, 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. additionAfter addition
  3. stirringthe mixture was stirred at −78° C. for 2 hours
  4. stirringThe mixture was stirred at −78° C. for another 40 minutes
  5. extractionAfter extracted with EtOAc (25 mL×3)
  6. washthe combined organic layers were washed with brine (50 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe obtained solid was recrystallized with EtOAc and petroleum ether

出典と根拠

ORDレコード
ord-38aa5c151105418d8d4f79442f276d6f
出典データセット
uspto-grants-2016_02
特許番号
US09265773B2

反応ノート

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