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

HRID 746613Notes

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.[N:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[CH:35]=[O:36]>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:35]([C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][N:29]=1)[OH:36]

Participants

Conditions

Temperature: -78 °C

Procedure

To a cooled (−78° C.) solution of [2-(3-bromo-benzo[b]thiophen-2-yl)-ethyl]-dimethyl-amine (800 mg, 2.8 mmol) in anhydrous toluene (30 mL), TMEDA (420 uL, 2.8 mmol) was added followed by nBuLi (2.1 mL, 2.6 mmol, 1.6M in hexanes). The mixture was stirred for 40 min at −78° C. and pyridine-2-carbaldehyde (800 uL, 8.4 mmol) was added. The mixture was stirred for 6 hrs during which the temperature reached 0° C., quenched with sat NH4Cl/NaHCO3 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 94/6) to afford [2-(2-dimethylamino-ethyl)-benzo[b]thiophen-3-yl]-pyridin-2-yl-methanol (Compound 13-1) (721 mg) in 82% yield. MH+=313.0, tR=2.49 min (Method 2).

Workup

additionwas added
stirringThe mixture was stirred for 6 hrs during which the temperature
customreached 0° C.
customquenched with sat NH4Cl/NaHCO3
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 94/6)

Sources & evidence

ORD record: ord-0bb4af0985c949b08158a8c2c93e507c
Source dataset: uspto-grants-2008_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07393865B2

Reaction notes

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