Hydrochloric Acid → HCID 66743701, compound

Temperature

60 °C

To a solution of methyl 5-bromo-3-(ethylamino)thiophene-2-carboxylate (2.46 g, 9.31 mmol) in MeOH (30 mL) was added a solution of sodium hydroxide (1.12 g, 27.9 mmol) in water (15 mL). After stirring at 60° C. for 4 h, 6 M aqueous HCl (2.9 mL) was added to the mixture to adjust the pH to 10. After removal of the solvent at reduced pressure, the residue was diluted with DMF (70 mL). Then, triethylamine (25.8 mL, 186 mmol) and ammonium chloride (10.0 g, 186 mmol) were added. After stirring at room temperature for 10 min, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (10.7 g, 55.9 mmol) and 1-hydroxybenzotriazole (7.55 g, 55.9 mmol) were added to the mixture and the stirring was continued for 17 h. Then, water and EtOAc were added to quench the reaction. The organic materials were extracted with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, hexane to 70:30 hexane/EtOAc) to give the title compound (0.97 g, 42%) as a pale green solid:

1. customAfter removal of the solvent at reduced pressure
2. additionthe residue was diluted with DMF (70 mL)
3. stirringAfter stirring at room temperature for 10 min
4. waitthe stirring was continued for 17 h
5. customto quench
6. customthe reaction
7. extractionThe organic materials were extracted with EtOAc
8. washThe combined extracts were washed with water and brine
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. customAfter removal of the solvent at reduced pressure
12. customthe residue was purified by column chromatography (Purif, silica gel, hexane to 70:30 hexane/EtOAc)

ORD record

ord-9e883e0573d64b43a9973d8a0238c272

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691828B2