Boron Trichloride → 4-Hydroxy-2-methylbenzonitrile

Boron trichloride (1M in dichloromethane, 747 ml, 747 mmol) was added dropwise, at −78° C., to a suspension of commercially available 4-methoxy-2-methyl-benzonitrile (44 g, 298 mmol) and tetrabutylammonium iodide (121 g, 327 mmol) in dichloromethane (750 ml), under nitrogen, over 40 minutes. Once the addition was complete, the yellow solution was warmed to room temperature and stirred for 16 hours at room temperature. The reaction mixture was then quenched by dropwise addition of water maintaining the internal temperature below 10° C. The mixture was filtered through Arbocel™ and the layers were separated. The aqueous layers were extracted again with dichloromethane (250 ml). The organic layers were combined, washed with a sodium thiosulphate solution (150 ml), dried over magnesium sulphate, filtered and concentrated under reduced pressure to give thick yellow oil. Trituration of the oil in dichloromethane, followed by filtration, provided a first crop of the title compound (10.8 g, 27%) as a white solid. The filtrate was evaporated and purified by flash chromatography on silica gel, eluting with pentane:ethyl acetate (70:30, by volume) to provide more of the title compound as a white solid (14.4 g, 36%). 1H-NMR (400 MHz, CDCl3): δ=2.46 (s, 3H), 6.68 (d, 1H), 6.72 (s, 1H), 7.45 (d, 1H); LRMS: APCl−: m/z 132 [M−H]−.

1. additionOnce the addition
2. customThe reaction mixture was then quenched by dropwise addition of water maintaining the internal temperature below 10° C
3. filtrationThe mixture was filtered through Arbocel™
4. customthe layers were separated
5. extractionThe aqueous layers were extracted again with dichloromethane (250 ml)
6. washwashed with a sodium thiosulphate solution (150 ml)
7. dry with materialdried over magnesium sulphate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customto give thick yellow oil
11. filtrationTrituration of the oil in dichloromethane, followed by filtration

ORD record

ord-ad0555b613914e0a85d3913c513915a8

Source dataset

uspto-grants-2007_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07309712B2