2-Methylbenzenesulfonic acid → HCID 178469953, compound

Temperature

85 °C

A mixture of methyl 1-amino-4-fluoro-1H-pyrrole-2-carboxylate (0.980 g, 6.20 mmol), (E)-ethyl 3-ethoxyacrylate (1.25 g, 8.68 mmol) and toluenesulfonic acid (0.059 g, 0.310 mmol) in ethanol (15 mL) was heated at 85° C. for 2 h then at reflux (100° C. bath) for an additional 2 h. The mixture was cooled and concentrated to remove the ethanol/water and additional ethanol was added and reconcentrated. The process was repeated until all of the water had been removed then residue was dissolved in ethanol (15 mL) and sodium tert-butoxide (1.190 g, 12.39 mmol) was added to make orange clear solution. This mixture was heated at 85° C. for 1 h, then cooled and concentrated to remove the ethanol and the reaction mixture was neutralized with HCl in dioxane (0.5 mL of 4N solution) then concentrated to afford a tan semi solid. This material was slurried in water and stirred for 1 h and the resulting solid was collected and rinsed with water and filtered and dried to afford the title compound (740 mg, 3.30 mmol, 53.3% yield) as a light yellow solid. HPLC (condition B): retention time=3.57 min. LCMS (condition B): m/z 224.9 +ve.

1. temperatureat reflux (100° C. bath) for an additional 2 h
2. temperatureThe mixture was cooled
3. concentrationconcentrated
4. customto remove the ethanol/water and additional ethanol
5. additionwas added
6. customhad been removed
7. dissolutionresidue was dissolved in ethanol (15 mL)
8. temperatureThis mixture was heated at 85° C. for 1 h
9. temperaturecooled
10. concentrationconcentrated
11. customto remove the ethanol
12. concentrationthen concentrated
13. customto afford a tan semi solid
14. customthe resulting solid was collected
15. washrinsed with water
16. filtrationfiltered
17. customdried

ORD record

ord-52e787401c424ebe9af5928c19bd9de9

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09221826B2