3-Bromo-2,5-difluorobenzaldehyde synthesis

Yield:-

Reaction Conditions:

with water;hypophosphorous acid;acetic acid;sodium nitrite at 0 - 20; for 1 h;

Steps:

19.4
4.6 g of 4-amino-3-bromo-2,5-difluorobenzaldehyde, 110 ml_ glacial acetic acid, and 54 ml_ of hypophosphorous acid were placed under nitrogen in an oven-dried flask and chilled to 0⁰C. 1.96 g of sodium nitrite dissolved with 11 ml_ water was added to the reaction mixture from an addition funnel maintaining reaction temperature below 15°C. The mixture was warmed to room temperature and stirred for 1 hour, diluted into 300 ml_ of ice water and extracted 3 times with methylene chloride. The combined organic layers were extracted with water, 2 times with 10% sodium hydroxide, 2 times with water, dried over sodium sulfate, filtered, concentrated, and purified by flash chromatography on silica. The product fractions were concentrated and dried under vacuum to give 2.79 g of product. GCMS (M)222; 1 H NMR (400 MHz, DMSO-c/6) δ ppm 7.66 (ddd, J=8.06, 4.83, 3.22 Hz, 1 H) 8.12 (ddd, J=7.52, 5.37, 3.22 Hz, 1 H) 10.13 (d, J=2.42 Hz, 1 H).

References:

PFIZER INC. WO2009/69044, 2009, A1 Location in patent:Page/Page column 91-92