Potassium Carbonate → HCID 21023788, compound

Temperature

120 °C

4-(2,2-Dimethoxyethoxy)-1,2-difluorobenzene Bromoacetaldehyde dimethyl acetal (3.3 ml, 27.9 mmol) and potassium carbonate (6.5 g, 47.1 mmol) were added to a solution of 3,4-difluorophenol (3.0 g, 23.4 mmol) in DMF (65 ml). The mixture was heated to 120° C. for 4 hours, cooled to room temperature and then quenched with a solution of aqueous ammonium chloride. The product was extracted into ethyl acetate, washed with water and brine, dried over magnesium sulphate, filtered and concentrated in vacuo to yield the title compound (5.1 g, 97%); 1H NMR (CDCl3) 3.45 (6H, s), 3.93 (2H, d, J 5.1 Hz), 4.67 (1H, t, J 5.1 Hz), 6.60 (1H, m), 6.74 (1H, m) and 7.03 (1H, m). Step 2. (3,4-Difluorophenoxy)-acetaldehyde A solution containing the product from Step 1 (5.1 g, 23.4 mmol), glacial acetic acid (4.5 ml) and concentrated sulphuric acid (2.7 ml) in water (50 ml) was heated at 100° C. for 5 hours. After cooling to room temperature, the product was extracted into diethyl ether. The organic extract was washed with aqueous sodium hydrogen carbonate solution, dried over magnesium sulphate, filtered an concentrated in vacuo. The product was purified by silica gel chromatography eluting with ethyl acetate:hexane (30:70) to yield the title compound (2.74 g, 68%); 1H NMR (CDCl3) 4.52 (2H, s), 6.59 (1H, m), 6.83 (1H, m), 7.08 (1H, m) and 9.82 (1H, s).

1. temperaturecooled to room temperature
2. customquenched with a solution of aqueous ammonium chloride
3. extractionThe product was extracted into ethyl acetate
4. washwashed with water and brine
5. dry with materialdried over magnesium sulphate
6. filtrationfiltered
7. concentrationconcentrated in vacuo

ORD record

ord-aad96bf977ce4c49b45440237ba34bba

Source dataset

uspto-grants-2006_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07026336B1