Hydrochloric Acid → HCID 71226916, compound

Temperature

55 °C

To a stirred solution of 3-chloro-4-(ethoxycarbonyl)-5-methylthiophene-2-carboxylic acid (F-5) (7.79 g, 31.3 mmol, 1.0 eq) in AcOH (150 mL) at RT, HgO (7.46 g, 34.4 mmol, 1.1 eq) is added and the resulting mixture is stirred at reflux for 1 h. The reaction mixture is cooled to 50-60° C. and then aqueous HCl (750 mL, 2.4 M, 1.8 mol) is added. The resulting mixture is stirred at reflux for an additional 1 h. The mixture is allowed to cool to RT and extracted with methyl tert-butyl ether (3×200 mL). The combined organic layers are washed with sat. NaHCO3 solution (3×200 mL), H2O (200 mL) and brine H2O (200 mL) sequentially. The organic layer is dried over anhydrous Na2SO4 and filtered. The filtrate is concentrated in vacuo and the residue is purified by flash column chromatography on silica gel (2% ethyl acetate-petroether) to afford the product, ethyl 4-chloro-2-methylthiophene-3-carboxylate (F-6).

1. temperatureat reflux for 1 h
2. stirringThe resulting mixture is stirred
3. temperatureat reflux for an additional 1 h
4. temperatureto cool to RT
5. extractionextracted with methyl tert-butyl ether (3×200 mL)
6. washThe combined organic layers are washed with sat. NaHCO3 solution (3×200 mL), H2O (200 mL) and brine H2O (200 mL) sequentially
7. dry with materialThe organic layer is dried over anhydrous Na2SO4
8. filtrationfiltered
9. concentrationThe filtrate is concentrated in vacuo
10. customthe residue is purified by flash column chromatography on silica gel (2% ethyl acetate-petroether)

ORD record

ord-ecf2a192f6494941b11a382f6bd0991b

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08969363B2