3-Butynoic acid, 4-(2-aMino-4-fluoro-5-nitrophenyl)-2,2-diMethyl-, phenylMethyl ester synthesis

Yield:1225589-66-1 56%

Reaction Conditions:

with triethylamine;bis-triphenylphosphine-palladium(II) chloride;copper(l) iodide at 20 - 80;

Steps:

11.a

To a solution of 2-bromo-5-fluoro-4-nitroaniline (23.0 g, 0.1 mol) in Et₃N (250 mL) was added benzoic 2,2-dimethylbut-3-ynoic anhydride (59.0 g, 0.29 mol), CuI (1.85 g) andPd(PPh₃)₂Cl₂ (2.3 g) at room temperature. The mixture was stirred at 8O⁰C overnight. After cooling to room temperature, the reaction was quenched with water and the aqueous layer was extracted with ethyl acetate (100 mL x 3). The combined organic layer was dried over anhydrous Na₂SO₄, the solvent was evaporated in vacuo. The residue was purified by chromatography on silica gel (10% ethyl acetate in petroleum ether) to give benzyl 4-(2-amino-4-fluoro-5- nitrophenyl)-2,2-dimethylbut-3-ynoate (20.0 g, 56%). ¹H NMR (400 MHz, CDCl₃) 8.05 (d, J = 8.4 Hz, 1 H), 7.39-7.38 (m, 5 H), 6.33 (d, J = 13.2 Hz, 1 H), 5.20 (s, 2 H), 4.89 (br s, 2 H), 1.61 (s, 6 H).

References:

WO2010/53471,2010,A1 Location in patent:Page/Page column 60-61