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

HRID 746630노트

반응식

HRID 746630 반응식
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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 1140Toluene용매

반응 조건

온도
-78 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-bca8a9b76a954dae91ffeb10bff6d093
출처 데이터셋
uspto-grants-2008_07
특허 번호
US07393865B2

반응 노트

불러오는 중…