Hydrochloric Acid → 3-Amino-5-bromothiophene-2-carboxamide

Temperature

70 °C

A mixture of methyl 3-amino-5-bromothiophene-2-carboxylate (5.67 g, 24.0 mmol) was mixed with sodium hydroxide (2.94 g, 73.6 mmol), MeOH (100 mL) and water (25 mL) was stirred at 70° C. overnight. After cooling to 0° C., 6 M HCl (8.17 mL, 49.0 mmol) was added. This mixture was concentrated under reduced pressure to give a yellow solid. Co-evaporation was carried out with toluene and the resulting solid was dried under reduced pressure well. This residue was mixed with ammonium chloride (26.3 g, 491 mmol), triethylamine (49.7 g, 491 mmol) and DMF (230 mL). After stirred at room temperature for 5 min, 1-hydroxybenzotriazole (19.9 g, 144 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (28.2 g, 147 mmol) were added. The stirring was continued for 2 days. The reaction mixture was poured into saturated aqueous NaHCO3 (700 mL) and extracted with EtOAc (700 mL), and the extract was washed with saturated aqueous NaHCO3, dried over MgSO4, filtered and concentrated under reduced pressure. The residual brown oil was purified by column chromatography (Purif, silica gel, hexane to EtOAc) to afford the title compound (4.05 g, 75%) as yellow solid:

1. temperatureAfter cooling to 0° C.
2. concentrationThis mixture was concentrated under reduced pressure
3. customto give a yellow solid
4. customCo-evaporation
5. customthe resulting solid was dried under reduced pressure well
6. stirringAfter stirred at room temperature for 5 min
7. waitThe stirring was continued for 2 days
8. extractionextracted with EtOAc (700 mL)
9. washthe extract was washed with saturated aqueous NaHCO3
10. dry with materialdried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. customThe residual brown oil was purified by column chromatography (Purif, silica gel, hexane to EtOAc)

ORD record

ord-d5619da5ca724f4b88a81d656a12c4b7

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691828B2