Formaldehyde → 2-(Hydroxymethyl)-4-(trifluoromethyl)phenol

Paraformaldehyde (3.4 g, 0.114 mol) was added in 0.5 g portions over a six hour period to a refluxing mixture of 4-trifluoromethyl phenol (2.3 g, 0.0142 mol), phenyl boronic acid (2.1 g, 0.017 mol) and proprionic acid (530 μL, 7 mmol) in benzene with the azeotropic removal of water (Dean-Stark trap). When the addition was complete, the reaction was heated for an additional hour, then cooled with an ice bath, diluted with THF (30 mL) and treated with 5 mL of 30% hydrogen peroxide solution. After stirring for one hour, the mixture was partitioned between water (50 mL) and ethyl acetate (50 mL). The organic layer was washed with NaHSO3 solution (1×50 mL), brine (1×50 mL), dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography (30% ethyl acetate/hexanes) to afford 950 mg (35%) of the title compound as a colorless solid. 1H NMR (400 MHz, CDCl3) δ 7.42 (d, 1H, J=9.1 Hz); 7.3 (s, 1H); 6.95 (d, 1H, J=9.1 Hz); 4.89 (s, 2H);

1. additionWhen the addition
2. temperaturethe reaction was heated for an additional hour
3. temperaturecooled with an ice bath
4. customthe mixture was partitioned between water (50 mL) and ethyl acetate (50 mL)
5. washThe organic layer was washed with NaHSO3 solution (1×50 mL), brine (1×50 mL)
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified by flash chromatography (30% ethyl acetate/hexanes)

ORD record

ord-81500cb4265c40f2b2387409994cb0c0

Source dataset

uspto-grants-2004_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06803457B1