Hydrochloric Acid → N-Benzyl-2-butanamidothiophene-3-carboxamide

Temperature

0 °C

A solution of tert-butyl 3-[(benzylamino)carbonyl]thien-2-ylcarbamate (2-2, 500 mg, 1.50 mmol, 1 equiv) was saturated with HCl gas at 0° C., and the resulting solution was stirred at 0° C. for 1 h, then allowed to warm to 23° C. and stirred for 1 h. The reaction mixture was concentrated and the residue was dissolved in pyridine (10 mL). The resulting solution was cooled to 0° C., and butyryl chloride (420 μL, 4.04 mmol, 2.69 equiv) was added in three equal portions over 1 h. The reaction mixture was partitioned between aqueous sodium bicarbonate solution and ethyl acetate (50 mL). The organic layer was dried over sodium sulfate and concentrated. The residue was purified by flash column (hexanes initially, grading to 100% ethyl acetate) to give N-benzyl-2-(butyrylamino)thiophene-3-carboxamide (2-3) as an off-white solid. 1H NMR (300 MHz, CDCl3) δ 7.36 (m, 5H), 6.92 (d, 1H, J=6.1 Hz), 6.76 (d, 1H, J=5.8 Hz), 6.23 (s, 1H), 4.62 (d, 2H, J=5.8 Hz), 2.47 (t, 2H, J=7.3 Hz), 1.80 (sextet, 2H, J=7.3 Hz), 1.01 (t, 3H, J=7.3 Hz).

1. temperatureto warm to 23° C.
2. stirringstirred for 1 h
3. concentrationThe reaction mixture was concentrated
4. dissolutionthe residue was dissolved in pyridine (10 mL)
5. temperatureThe resulting solution was cooled to 0° C.
6. customThe reaction mixture was partitioned between aqueous sodium bicarbonate solution and ethyl acetate (50 mL)
7. dry with materialThe organic layer was dried over sodium sulfate
8. concentrationconcentrated
9. customThe residue was purified by flash column (hexanes initially

ORD record

ord-8857268847584232b07a5517365ca386

Source dataset

uspto-grants-2008_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07378411B2