8-broMo-2,4-dichloro-7-Methoxyquinoline synthesis

Yield:1254256-54-6 90%

Reaction Conditions:

with N-Bromosuccinimide;trifluoroacetic acid in dichloromethane at 0 - 20; for 2 h;

Steps:

2

Step 2 - Preparation of 8-bromo-2,4-dichloro-7-methoxy-quinoline1. Charged 2,4-dichloro-7-methoxy quinoline (31.05 g, 136 mmol) and methylene chloride (620 mL).2. Cooled the mixture to 0⁰C and charged TFA (2.5 eq) and NBS (1.15 eq) and then warmed the mixture to room temperature.3. Stirred at room temperature for 2h.4. Quenched with IM NaOH (~ 349 mL, 40 mmol) to adjust the pH to 7 and separated the layers.5. Washed with water (403 mL) and allowed the layers to separate. Collected organic layer.6. Distilled solvent using rotovap under reduced pressure and solvent switched to IPA (250 mL).7. Heated to 70⁰C and then cooled to 22°C over 2h and treated with IM NaOH (88mL, 0.5eq) at room temperature and stirred for 30 min.8. Filtered and rinsed with 1 :3 mixture of IP A/Water (100 mL) and water (250 mL) and dried under vacuum at 50⁰C to afford 37.62 g of product (90% yield) as beige/tan solid. HPLC area % purity: ~ 95.1%.

References:

WO2010/129451,2010,A1 Location in patent:Page/Page column 11-12