2-Bromo-5-fluoropyridine → 1-[2-(2-Dimethylamino-ethyl)-benzo[b]thiophen-3-yl]-1-(5-fluoro-pyridin-2-yl)-ethanol

HRID 746610Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1.C([Li])CCC.[CH3:14][N:15]([CH3:30])[CH2:16][CH2:17][C:18]1[S:22][C:21]2[CH:23]=[CH:24][CH:25]=[CH:26][C:20]=2[C:19]=1[C:27](=[O:29])[CH3:28]>C(Cl)Cl.CCCCCC>[CH3:30][N:15]([CH3:14])[CH2:16][CH2:17][C:18]1[S:22][C:21]2[CH:23]=[CH:24][CH:25]=[CH:26][C:20]=2[C:19]=1[C:27]([C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1)([OH:29])[CH3:28]

Participants

Conditions

Temperature: -78 °C

Procedure

2-Bromo-5-fluoropyridine (5 g, 0.03 mol) was dissolved in methylene chloride (18 mL) and was cooled at −78° C. 1.6 M of n-butyllithium in hexane (18 mL) was added dropwise in 5 minutes and the reaction was stirred for 120 minutes at −78° C. Then a solution of 1-[2-(2-dimethylamino-ethyl)-benzo[b]thiophen-3-yl]-ethanone (1.75 g, 7.1 mmol) dissolved in methylene chloride (9 mL) and added dropwise and the mixture was allowed to warm to room temperature gradually overnight. The reaction was quenched with aq NH4Cl, followed by water and ammonium hydroxide. The organic layer was extracted with Methylene chloride, and dried over sodium sulfate. Silica gel column chromatography (eluent: 9:1 DCM/MeOH) afforded 1.656 g of 1-[2-(2-dimethylamino-ethyl)-benzo[b]thiophen-3-yl]-1-(5-fluoro-pyridin-2-yl)-ethanol (Compound 7-1) (68%).

Workup

additionadded dropwise
temperatureto warm to room temperature gradually overnight
customThe reaction was quenched with aq NH4Cl
extractionThe organic layer was extracted with Methylene chloride
dry with materialdried over sodium sulfate

Sources & evidence

ORD record: ord-c943a41a518b4051a54dbf38a5c7372e
Source dataset: uspto-grants-2008_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07393865B2

Reaction notes

Loading…