1-(5-Bromo-2,4-difluoro-phenyl)-ethanone synthesis

Yield: 41%

Reaction Conditions:

Stage #1:2,4-difluorobromobenzene;acetyl chloride with aluminum (III) chloride at 60 - 95; for 10 h;Friedel Crafts Acylation;
Stage #2: at -10; for 1 h;

Steps:

A19
Example A19Preparation of intermediate 19: l-(5-bromo-2,4-difluoro-phenyl)-ethanoneA mixture of A1C1₃ (200 g, 1515.1 mmol) in l-bromo-2,4-difluoro-benzene (120 g, 621.79 mmol) was stirred at 60 °C for 10 minutes. Then, acetyl chloride (73 g,929.9 mmol) was added dropwise over 4 hours and the mixture stirred at 95 °C for 6 hours. The mixture was cooled at - 10 °C and ice (300 g) was added over 1 hour. Then, AcOEt was added (500 mL) and the separated organic layer was washed with water, dried (Na₂S0₄), filtered and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel; AcOEt in heptane 1/50). The desired fractions were collected and concentrated in vacuo to yield intermediate 19 (60 g, 41% yield).

References:

JANSSEN PHARMACEUTICA NV;TRABANCO-SUÁREZ, Andrés, Avelino;TRESADERN, Gary, John;MACDONALD, Gregor, James;VEGA RAMIRO, Juan, Antonio WO2011/154374, 2011, A1 Location in patent:Page/Page column 26