Hydrochloric Acid → 4-Fluoro-2-hydroxybenzaldehyde

To the mixture of 3-fluorophenol (10 mL, 102 mmol), anhydrous magnesium chloride (28.2g, 744.6 mmol) in 500 mL of anhydrous acetonitrile was added anhydrous triethylamine (67 mL, 382.5 mmol) and paraformaldehyde (22.3g, 744.6 mmol). The mixture was then heated to reflux for five hrs. After cooling to room temperature, 500 mL of 5% aqueous hydrochloric acid was added. The product was extracted with ethyl acetate. The combined organic extracts were washed three times with 5% hydrochloric acid, brine, and dried over anhydrous magnesium sulfate. After removing the volatiles, the product was obtained as a light pink solid; 11 g, yield=72%. A small fraction was further purified on silica gel column with EtOAc/hexane mixture for further analytical characterization, it gave a white solid. M.P.=67.5-69.0° C. 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). 13C(CDCl3/30OMH) 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). LC-MS couldn't observe the desired peak. HRMS (ES−) m/z calcd for (C7H5FO2) 139.0201 (M−H), found 139.0211(M−H).

1. temperatureThe mixture was then heated
2. temperatureto reflux for five hrs
3. extractionThe product was extracted with ethyl acetate
4. washThe combined organic extracts were washed three times with 5% hydrochloric acid, brine
5. dry with materialdried over anhydrous magnesium sulfate
6. customAfter removing the volatiles
7. customthe product was obtained as a light pink solid
8. customA small fraction was further purified on silica gel column with EtOAc/hexane mixture for further analytical characterization, it
9. customgave a white solid

ORD record

ord-78dc4d9a67e24e2da1bd6120da77a9f7

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07259266B2