4-Ethoxy-3,5-difluorobenzoicacid synthesis

Yield:1017779-19-9 69%

Reaction Conditions:

with sodium hydride in N,N-dimethyl-formamide;mineral oil at 0; for 1 h;

Steps:

D111 4-Ethoxy-3,5-difluorobenzoicacid

To a solution of 3,4,5-trifluorobenzoic acid (5.28 g, 3.0 mmol) and ethanol (1.38 g, 3 mmol) in DMF (50 mL) was added NaH (4.8 g, 12.0 mmol, 60% w/t in mineral oil) at 0 °C . Then, the reaction mixture was stirred for lh, and then concentrated. The residue was dissolved in water and adjusted pH to lower than 7 with IN HCl, and then extracted with EtOAc. The EtOAc solution was washed with brine, dried over sodium sulphate, and concentrated. The residue was purified by FC (PE/EtOAc =4: 1) to afford the title compound (4.2 g, 69%) as a white solid. NMR (300MHz, CDC13) δ: 7.67 (1H), 7.65 (1H), 4.37 (2H), 1.43 (3H).

References:

WO2014/114249,2014,A1 Location in patent:Page/Page column 46