Dimethylformamide → 5-Hydroxymethyl-2,4-dimethoxy-benzonitrile

Temperatur

90 °C

To a solution of (5-bromo-2,4-dimethoxy-phenyl)-methanol (2.75 g, 11.13 mmol) in dimethylformamide (15 mL) at room temperature was added zinc cyanide (784 mg, 6.678 mmol). The reaction mixture was degassed by passing argon through for 2 h before tetrakis(triphenylphosphine)palladium (772 mg, 0.668 mmol) was added. The reaction mixture was heated at 90° C. for 12 h. After the reaction mixture was cooled to room temperature, it was diluted with diethyl ether (100 mL) and washed with sodium bicarbonate solution, brine and dried over anhydrous sodium sulfate. The solid was filtered off and the filtrate was concentrated in vacuo. Purification of the crude residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel) eluting with 40-50% ethyl acetate in hexanes yielded 5-hydroxymethyl-2,4-dimethoxy-benzonitrile as a white solid (1.089 g, 51%).

1. customThe reaction mixture was degassed
2. customthrough for 2 h
3. additionwas added
4. temperatureAfter the reaction mixture was cooled to room temperature
5. washwashed with sodium bicarbonate solution, brine
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationThe solid was filtered off
8. concentrationthe filtrate was concentrated in vacuo
9. customPurification of the crude residue by flash chromatography (Biotage system, KP-Sil™ 32-63 μm, 60 Å silica gel)
10. washeluting with 40-50% ethyl acetate in hexanes

ORD-Eintrag

ord-0e8f45f7769e4baf95608373ce74b704

Quelldatensatz

uspto-grants-2003_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06617346B1