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

HRID 746630Notes

Reaction equation

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]

Participants

Conditions

Temperature: -78 °C

Procedure

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.

Workup

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)

Sources & evidence

ORD record: ord-bca8a9b76a954dae91ffeb10bff6d093
Source dataset: uspto-grants-2008_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07393865B2

Reaction notes

Loading…