4'-Hydroxyacetophenone → HCID 68406036, compound

Participants

Reaction Steps

A mixture of 2-(dimethylamino)ethyl chloride hydrochloride (1.05 g, 7.3 mmol) and 4-hydroxyacetophenone (1 g, 7.3 mmol) was dissolved in acetone (100 mL) followed by addition of anhydrous K2CO3 (10 g, 73 mmol). The reaction mixture was stirred at room temperature overnight, filtered, and the filtrate was concentrated in vacuo. The resulting residue was dissolved in THF (20 mL) and a portion of the obtained solution (7.4 mL, 2.7 mmol) was mixed with phenyltrimethylammonium tribromide (1.05 g, 2.7 mmol). The reaction mixture was heated at reflux for 1 h, cooled, and stirred at room temperature overnight, then concentrated in vacuo. The resulting residue was dissolved in water (15 mL) and extracted with dichloromethane (2×30 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo. The resulting crude bromoketone was dissolved in dry dioxane (25 mL), and a portion of the solution (1 mL, 0.11 mmol) was combined with (3-morpholin-4-yl-propyl)-thiourea (21 mg, 0.11 mmol). The reaction mixture was heated at 80° C. for 1 h, cooled, and stirred at room temperature overnight, then concentrated in vacuo. The resulting residue was suspended in dry chloroform (600 μL) followed by addition of N,N-diisopropylethylamine (52 μL, 0.3 mmol) and thiophene-2-carbonyl chloride (24 μL, 0.22 mmol). The reaction mixture was maintained for 30 min at room temperature, then concentrated in vacuo. The resulting residue was dissolved in AcOH (5 mL) and heated at reflux for 30 min, cooled, and concentrated in vacuo. The residue was dissolved in DMSO (600 μL) and portion of the solution (200 μL, 0.035 mmol) was subjected to HPLC purification (Method Z) to provide the title compound (0.8 mg) as a yellowish amorphous solid. LC/MS (ESI) m/z 501.1 [M+H]. HPLC retention time (Method B)=2.21 min.

Provenance & Evidence