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

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Reaktionsgleichung

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]

Komponenten

Reaktionsbedingungen

Temperatur: -78 °C

Versuchsvorschrift

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.

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag: ord-bca8a9b76a954dae91ffeb10bff6d093
Quelldatensatz: uspto-grants-2008_07
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US07393865B2

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