Methanol → Methyl 4-bromothiophene-2-carboxylate

To a cooled (−20° C.) solution of 6.02 g (29.1 mmol) of 4-bromothiophene-2-carboxylic acid (as prepared in the previous step) in 100 mL of anhyd MeOH under nitrogen was added 2.55 mL (34.9 mmol) of thionyl chloride dropwise at a rate to keep the temperature below −5° C. (ca. 8-10 min). After stirring for 1 h at room temperature, the mixture was refluxed for 8 h, cooled, and concentrated in vacuo. The resulting 6.7 g of pale amber oil was passed through a 150 g pad of silica gel with ca. 600 mL of CH2Cl2 (discarding the first 120 mL which contained a minor impurity) to afford, after concentration in vacuo, the title compound as a colorless oil (6.11 g, 95%). 1H-NMR (300 MHz, CDCl3) δ7.69 (d, 1H, J=1.5 Hz), 7.45 (d, 1H, J=1.5 Hz), and 3.90 (s, 3H).

1. customthe temperature below −5° C. (ca. 8-10 min)
2. temperaturethe mixture was refluxed for 8 h
3. temperaturecooled
4. concentrationconcentrated in vacuo
5. customto afford
6. concentrationafter concentration in vacuo

ORD record

ord-887f3ea1bed0465692a770e93b774114

Source dataset

uspto-grants-2002_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06492403B1