1-(4-BroMo-3-Methoxyphenyl)ethanone synthesis

Yield: 5.9 g

Reaction Conditions:

Stage #1:4-bromo-3-methoxyaniline with hydrogenchloride;sodium nitrite in water at -5 - 0; for 1 h;Sandmeyer Reaction;
Stage #2:sodium acetate with Acetaldehyde oxime;copper(II) sulfate in water at 0 - 10; for 2 h;
Stage #3: with hydrogenchloride in water for 2 h;Reflux;

Steps:

To a mixture of commercial 4-bromo-3-methoxyaniline (10.2 g, 50.6 mmoles) in HCl_cc/H₂O (11/25 mL) previously cooled to -5° C. there is added in portions NaNO₂ (3.48 g). The reaction mixture is stirred for 1 h at 0° C. before being transferred to a mixture of acetaldoxime (6.02 g), CuSO₄ (2.52 g), AcONa.3H₂O (36.64 g) in water (20.5 mL) at 0° C. The resulting mixture is stirred between 0° C. and 10° C. for 2 h, and then 37% HCl (23 mL) is added and the mixture is refluxed for 2 hours. After return to ambient temperature, the mixture is extracted with heptane, and the organic phase is dried over MgSO₄. Evaporation of the organic phase in vacuo yields a residue, which is chromatographed on silica gel (eluant CH₂Cl₂/cyclohexane (50/50 to 90/10)). Intermediate 681 (5.9 g) is obtained in the form of an amorphous solid. ¹H NMR (400 MHz; CDCl₃): δ 7.55 (d, 1H); 7.50 (d, 1H); 7.40 (dd, 1H); 3.95 (s, 3H); 2.60 (s, 3H). IR (cm^-1): 1681

References:

LES LABORATOIRES SERVIER;CHIMENTI, Stéfano;COURCHAY, Christine;DESSINGES, Aimee;GELLIBERT, Françoise;GOUMENT, Bertrand;KONNERT, Marc;PEGLION, Jean-Louis;POITEVIN, Christophe;VILAINE, Jean-Paul;VILLENEUVE, Nicole US2017/137385, 2017, A1 Location in patent:Paragraph 0260; 0261; 0262; 0263