3,3-Difluoro-2,2-diMethyl-1-indanone synthesis

Yield:-

Reaction Conditions:

with ethanol;diethylamino-sulfur trifluoride in chlorobenzene for 3 h;Heating / reflux;

Steps:

18.b
b) 3,3-Difluoro-2,2-dimethyl-indan-1 -one; To a solution of 2,2-dimethyl-indan-1 ,3-dione (770 mg, 4.42 mmol) in chlorobenzene (3 ml.) is added (diethylamino)sulfur trifluoride (2.9 mL, 22.1 mmol) followed by ethanol (52 μl_, 0.9 mmol) . The reaction is heated to reflux for 3 hours, at which time the mixture is cooled to room temperature and diluted with water and saturated aqueous NaHCO₃. The solution is extracted two times with ethyl acetate and the organic extracts are combined, dried with Na₂SO₄, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-heptane, 0:1 to 1 :10) to furnish 3,3-difluoro-2,2- dimethyl-indan-1-one; ¹H NMR (400 MHz, CDCI₃) δ ppm 1.31 (t, J=1.9 Hz, 6 H), 7.69 (t, J=7.3 Hz, 1 H), 7.78 - 7.89 (m, 3 H).

References:

NOVARTIS AG WO2008/76336, 2008, A2 Location in patent:Page/Page column 99-100