Methyl 3-amino-2-thiophenecarboxylate → 3-amino-N-(4-(trifluoromethoxy)phenyl)thiophene-2-carboxamide

To a stirred solution of 4-trifluoromethoxyaniline (7.8 g, 44.5 mmol) in toluene (50 mL) under nitrogen was added trimethylaluminum (2M in toluene, 26.7 mL, 53.4 mmol). The mixture was stirred at RT for 16 h. Methyl 3-amino-2-thiophenecarboxylate (7 g, 44.5 mmol) was added and the resulting solution was stirred at reflux (oil bath temperature: 130° C.) under nitrogen for 24 h. After cooling to RT, saturated sodium bicarbonate solution (100 mL) was added dropwise with caution and the mixture was stirred at RT for 30 min. The product was extracted into dichloromethane (3×100 mL), and the organic layer was dried over Na2SO4, and concentrated to yield a thick oil, which was then triturated with a mixture of hexane/ethyl acetate to afford N-(4-trifluoromethoxyphenyl) 3-Aminothiophene-2-carboxamide as a brown solid. 1H-NMR (400 MHz/CD3OD): δ=6.65 (d, J=5.6 Hz, 1H), 7.23 (d, J=8.4 Hz, 2H), 7.39 (d, J=5.2 Hz, 1H), 7.67 (d, J=9.2 Hz, 2H). MS (ES+): 303 [MH+].

1. stirringthe resulting solution was stirred
2. temperatureat reflux (oil bath temperature: 130° C.) under nitrogen for 24 h
3. temperatureAfter cooling to RT
4. stirringthe mixture was stirred at RT for 30 min
5. extractionThe product was extracted into dichloromethane (3×100 mL)
6. dry with materialthe organic layer was dried over Na2SO4
7. concentrationconcentrated
8. customto yield a thick oil, which
9. customwas then triturated with a mixture of hexane/ethyl acetate

ORD record

ord-8d9aaa7b9e764e2aaf2ad7c0cae5fcb7

Source dataset

uspto-grants-2005_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06949563B2