Formaldehyde → 2-Hydroxy-3-(trifluoromethoxy)benzaldehyde

A solution of 2-trifluoromethoxyphenol (5.13 g, 28.8 mmol) in anhydrous acetonitrile (150 mL) in oven-dried glassware was treated with triethylamine (15.0 mL, 108 mmol) and MgCl2 (4.11 g, 43.2 mmol) which had been dried under vacuum with heating. Paraformaldehyde (5.18 g, 172 mmol), which had been dried under vacuum with P2O5, was then added and the solution was heated to reflux. After 5 days, the reaction was quenched with 1 N HCl (200 mL). The mixture was extracted using Et2O (2×100 mL). The combined organics were washed with brine (2×150 mL), dried (Na2SO4) and concentrated to a yellow solid. Purification by column chromatography (silica gel, 98:2 to 95:5 hexanes/EtOAc) gave the title compound (2.45 g, 41%) as a yellow powder: 1H NMR (300 MHz, DMSO-d6) δ 10.24 (s, 1H), 7.75-7.65 (m, 2H), 7.08 (t, J=7.9 Hz, 1H).

1. customhad been dried under vacuum
2. temperaturewith heating
3. additionwas then added
4. temperaturethe solution was heated to reflux
5. customthe reaction was quenched with 1 N HCl (200 mL)
6. extractionThe mixture was extracted
7. washThe combined organics were washed with brine (2×150 mL)
8. dry with materialdried (Na2SO4)
9. concentrationconcentrated to a yellow solid
10. customPurification by column chromatography (silica gel, 98:2 to 95:5 hexanes/EtOAc)

ORD record

ord-d1447bba1f244ee19c78b968a9eddf49

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07879872B2