Iodine → (3-Ethoxy-4-methoxy-phenyl)-(4-methoxy-3-nitro-phenyl)-methanol

Grignard reagent was prepared in an oven-dried three necked flask outfitted with a reflux condenser, dropping funnel, and magnetic stirrer. Approximately ¼ of a solution of (3-ethoxy-4-methoxy-bromo)-benzene (10 g, 43.3 mmol) in anhydrous THF (60 mL) was added to a mixture of magnesium turnings (1.05 g, 43.3 mmol) in THF (10 mL) with a small piece of iodine. As soon as the solution became colorless (heating sometimes necessary), the remaining (3-ethoxy-4-methoxy-bromo)-benzene solution was added dropwise to the reaction mixture under mild reflux, over 30 min. The resulting mixture was refluxed for 3 h then cooled to room temperature for 30 min. The (3-ethoxy-4-methoxy-phenyl) magnesium bromide was then added slowly to a stirred solution of 4-methoxy-3-nitro-benzaldehyde (6.53 g, 36.1 mmol) in THF (60 mL) at 0° C. After complete addition, the reaction mixture was stirred at cold for 10 min and then at room temperature for 2 h. The solution was cooled to 0° C. and quenched with saturated NH4Cl solution (90 mL). The aqueous layer was extracted with ether (3×90 mL). The combined organic layers were washed with water (2×120 mL), brine (120 mL) and dried (MgSO4). Removal of solvent gave the crude (3-ethoxy-4-methoxy-phenyl)-(4-methoxy-3-nitro-phenyl) -methanol, which was used in the next step without further purification.

1. customan oven-dried three necked flask
2. customoutfitted with a reflux condenser
3. additionwas added dropwise to the reaction mixture under mild reflux, over 30 min
4. temperatureThe resulting mixture was refluxed for 3 h
5. additionAfter complete addition
6. waitat room temperature for 2 h
7. temperatureThe solution was cooled to 0° C.
8. customquenched with saturated NH4Cl solution (90 mL)
9. extractionThe aqueous layer was extracted with ether (3×90 mL)
10. washThe combined organic layers were washed with water (2×120 mL), brine (120 mL)
11. dry with materialdried (MgSO4)
12. customRemoval of solvent

ORD record

ord-c122ea9b53564a5d916fb4ea01f1030f

Source dataset

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07470723B2