2-BroMo-4-chloro-6-fluorobenzaldehyde synthesis

Yield: 95%

Reaction Conditions:

with isopropylmagnesium chloride in tetrahydrofuran;n-heptane at -40; for 0.5 h;Inert atmosphere;

Steps:

B-2.A
ΓΑ1 2-Bromo-4-chloro-6-fluoro-benzaldehydeTo a solution of l,2-dibromo-5-chloro-3-fluoro-benzene (10 g, 34.68 mmol) in heptane (27 ml) was added THF (44 ml) and the mixture was cooled to -45 °C. Then, iPrMgCl (38.14 ml, 38.14 mmol, 1M solution in THF) was added dropwise to the reaction mixture maintaining the temperature between -40 °C to -45° C. The mixture was stirred for 30 minutes at -40 °C before DMF (13.4 ml, 173.4 mmol) was added dropwise to the reaction mixture maintaining the temperature between -45 °C to -20 °C. After stirring for another 15 minutes at -20 °C, it was poured into a mixture of 2N HC1 (20 ml) and ether (50 ml) at 0 °C. The organic layer was separated and the aqueous layer was extracted two times with ether. The combined organic layers were dried with Na₂S0₄ and evaporated in vacuo to obtain the title compound (7.8 g, 95%) as yellow solid.

References:

F. HOFFMANN-LA ROCHE AG;AEBI, Johannes;BINGGELI, Alfred;HERTEL, Cornelia;KONKAR, Anish Ashok;KUEHNE, Holger;KUHN, Bernd;MAERKI, Hans P.;WANG, Haiyan WO2012/101011, 2012, A2 Location in patent:Page/Page column 68-69