Hydrochloric Acid → 4-Fluoro-2-hydroxybenzaldehyde

To the mixture of 3-fluorophenol (10 mL, 102 mmole), anhydrous magnesium chloride (28.2 g, 744.6 mmole) in 500 mL of anhydrous acetonitrile was added anhydrous triethylamine (67 mL, 382.5 mmole) and paraformaldehyde (22.3 g, 744.6 mmole). The mixture was then heated to reflux for five hours. After cooling to r.t, 500 mL of 5% aqueous hydrochloric acid was added. The product was extracted with ethyl acetate. The combined organic extracts were washed with 5% hydrochloric acid (×3), brine, and dried over anhydrous magnesium sulfate. After removing the volatiles, the residue was a light pink solid. 11 g, yield 72%. M.P: 67.5-69.0° C. ESHRMS m/z 139.0211(M−H, C7H4FO2 calc'd 139.0201). 1H NMR (CDCl3/300 MHz) 11.40 (s, 1H), 9.86 (s, 1H), 7.62-7.57 (m, 1H ), 6.79-6.67 (m, 2H). 3C (CDCl3/300 MH) 195.4, 168.3 (d, J=258 Hz), 164.4 (d, J=14.9 Hz), 136.3 (d, J=12.6 Hz), 118.2 (d, J=2.0 Hz), 108.5 (d, J=23.3 Hz), 104.9 (d, J=24.4 Hz). 19F (CDCl3/400 MHz) −97.9 (m).

1. temperatureThe mixture was then heated
2. temperatureto reflux for five hours
3. temperatureAfter cooling
4. extractionThe product was extracted with ethyl acetate
5. washThe combined organic extracts were washed with 5% hydrochloric acid (×3), brine
6. dry with materialdried over anhydrous magnesium sulfate
7. customAfter removing the volatiles

ORD record

ord-50128a1875cc4a91a17539aca5e52c76

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07259266B2