Hydrochloric Acid → 6-(5-Methylthiophen-2-yl)-5-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)naphthalen-2-ol

Temperature

0 °C

Dissolve 1-(2-(4-(6-methoxy-2-(5-methylthiophen-2-yl)naphthalen-1-yloxy)phenoxy)ethyl)piperidine hydrochloride (5.15 g, 10.1 mmol) in dichloromethane (340 mL). Cool the resulting solution to 0° C. In a separate container under nitrogen combine neat boron tribromide (3.9 mL, 40.4 mmol) and dichloromethane (36.5 mL). Add the resulting boron tribromide solution to the cooled solution. Stir the resulting mixture at 0° C. for 2.5 hours. Quench the mixture with saturated aqueous sodium bicarbonate and allow it to warm to room temperature. Separate the layers and extract the aqueous layer with 20% methanol in dichloromethane (10 mL×3). Concentrate the combined organic solutions to give a solid. Slurry the solid in methanol (234 mL) and add HCl (1N in water; 10.8 mL). Load the resulting solution onto an SCX acidic ion exchange column. Flush the column with 40% methanol in dichloromethane then elute desired material with 40% 7M ammonia in methanol in dichloromethane. Concentrate the ammonia containing eluent to give the title compound (4.54 g, 9.88 mmol). LRMS (m/z): 460 (M+1).

1. customQuench the mixture with saturated aqueous sodium bicarbonate
2. temperatureto warm to room temperature
3. customSeparate the layers
4. extractionextract the aqueous layer with 20% methanol in dichloromethane (10 mL×3)
5. concentrationConcentrate the combined organic solutions
6. customto give a solid
7. customFlush the column with 40% methanol in dichloromethane
8. washthen elute desired material with 40% 7M ammonia in methanol in dichloromethane
9. concentrationConcentrate the ammonia containing eluent

ORD record

ord-fc3e2b0bee684886893e0407ba759dda

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08476300B2