N,N,N',N'-Tetramethylethylenediamine → [2-(2-Dimethylamino-ethyl)-benzo[b]thiophen-3-yl]-(2-fluoro-pyridin-3-yl)-methanol

HRID 746630ノート

反応式

HRID 746630 の反応式
Br[C:2]1[C:3]2[CH:15]=[CH:14][CH:13]=[CH:12][C:4]=2[S:5][C:6]=1[CH2:7][CH2:8][N:9]([CH3:11])[CH3:10].CN(CCN(C)C)C.[Li]CCCC.[F:29][C:30]1[C:35]([CH:36]=[O:37])=[CH:34][CH:33]=[CH:32][N:31]=1>C1(C)C=CC=CC=1>[CH3:10][N:9]([CH3:11])[CH2:8][CH2:7][C:6]1[S:5][C:4]2[CH:12]=[CH:13][CH:14]=[CH:15][C:3]=2[C:2]=1[CH:36]([C:35]1[C:30]([F:29])=[N:31][CH:32]=[CH:33][CH:34]=1)[OH:37]

参加物

6

反応物 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 114349442-Fluoropyridine-3-carbaldehydeHCID 58591562[2-(3-Bromo-benzo[b]thiophen-2-yl)-ethyl]-dimethyl-amineHCID 178418339Butyllithium

生成物 1

HCID 58591576[2-(2-Dimethylamino-ethyl)-benzo[b]thiophen-3-yl]-(2-fluoro-pyridin-3-yl)-methanol収率 26%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

反応条件

温度
-78 °C

実験手順

To a cooled (−78° C.) solution of [2-(3-bromo-benzo[b]thiophen-2-yl)-ethyl]-dimethyl-amine (400 mg, 1.4 mmol) in anhydrous toluene (16 mL), TMEDA (240 uL, 2.8 mmol) was added followed by nBuLi (1.0 mL, 1.7 mmol, 1.6M in hexanes). The mixture was stirred for 40 min at −78° C. and 2-fluoro-3-pyridine-carbaldehyde (0.70 g, 5.6 mmol) was added. The mixture was stirred for 12 hrs during which the mixture warmed up to room temperature, quenched with 1M HCl (2 mL) and extracted with EtOAc (3×). The combined organic layers were dried (Na2SO4), concentrated and purified by silical gel column chromatography (gradient of DCM/MeOH=98/2 up to 90/10) to afford [2-(2-dimethylamino-ethyl)-benzo[b]thiophen-3-yl]-(2-fluoro-pyridin-3-yl)-methanol (Compound 24-1) (0.12 g) in 26% yield. MH+=331.0.

後処理

  1. additionwas added
  2. stirringThe mixture was stirred for 12 hrs during which the mixture
  3. temperaturewarmed up to room temperature
  4. customquenched with 1M HCl (2 mL)
  5. extractionextracted with EtOAc (3×)
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. concentrationconcentrated
  8. custompurified by silical gel column chromatography (gradient of DCM/MeOH=98/2 up to 90/10)

出典と根拠

ORDレコード
ord-bca8a9b76a954dae91ffeb10bff6d093
出典データセット
uspto-grants-2008_07
特許番号
US07393865B2

反応ノート

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