Methanol → Methyl 2-Bromo-4-chlorobenzoate

To a 500 ml 2 necked RB flask containing anhydrous methanol (300 ml) was added thionyl chloride (29.2 ml, 400 mmol) dropwise at 0-5° C. (ice water bath) over 10 min. The ice water bath was removed, and 2-bromo-4-chloro-benzoic acid (25 g, 106 mmol) was added. The mixture was heated to mild reflux for 12 h. Progress of the reaction was monitored by TLC and LCMS. After completion of the reaction, the reaction mixture was concentrated. Crude product was dissolved in dichloromethane (DCM, 250 ml), washed with water (50 ml), sat. aq. NaHCO3 (50 ml), brine (50 ml), dried over sodium sulfate, and concentrated to give the 2-bromo-4-chloro-benzoic acid methyl ester (26 g, 99%), which was directly used in the following step.

1. customThe ice water bath was removed
2. temperatureThe mixture was heated
3. temperatureto mild reflux for 12 h
4. customAfter completion of the reaction
5. concentrationthe reaction mixture was concentrated
6. dissolutionCrude product was dissolved in dichloromethane (DCM, 250 ml)
7. washwashed with water (50 ml), sat. aq. NaHCO3 (50 ml), brine (50 ml)
8. dry with materialdried over sodium sulfate
9. concentrationconcentrated

ORD record

ord-12c03a43809e4f82a399c578704bbfa4

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08772482B2