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 heat. Paraformaldehyde (5.18 g, 172 mmol), which had been dried under vacuum with P2O5, was added and the solution was heated to reflux. After 5 days, the reaction was quenched with 1 N HCl (200 mL) and 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 heat
3. additionwas 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-6a7d0b11439e4253be113ee5f7269801

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08450307B2