Pyridine → N-butyl-4-cyano-2-methyl-benzamide

To a solution of 4-cyano-2-methyl-benzoic acid (1.209 g, 7.5 mmol) (Example I1) and N,N-dimethylformamide (“DMF”) (2 drops) in dichloromethane (40 ml) under an atmosphere of nitrogen was added oxalyl chloride (0.95 ml, 11.25 mmol). The reaction mixture was stirred for one hour at ambient temperature and then at 60° C. for 1.5 hours. The reaction mixture was concentrated and the residue dissolved in tetrahydrofuran (50 ml). The solution was added drop-wise to a solution of n-butylamine (1.48 mg, 15 mmol) and pyridine (1.81 ml, 22.50 mmol) in tetrahydrofuran (50 ml). The reaction mixture was stirred at ambient temperature for 4 hours. Then the reaction mixture was poured into aqueous sodium hydrogen carbonate (1M) and the mixture extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated. The residue was purified by column chromatography (eluent: ethyl acetate/cyclohexane 1:2) to give N-butyl-4-cyano-2-methyl-benzamide (0.92 g, 57% yield). 1H-NMR (400 MHz, CDCl3): 0.97 (3H, t), 1.42 (2H, m), 1.62 (2H, m), 2.48 (3H, s), 3.45 (2H, q), 5.73 (1H, s), 7.41 (1H, d), 7.48-7.51 (2H, m) ppm.

1. waitat 60° C. for 1.5 hours
2. concentrationThe reaction mixture was concentrated
3. dissolutionthe residue dissolved in tetrahydrofuran (50 ml)
4. stirringThe reaction mixture was stirred at ambient temperature for 4 hours
5. extractionthe mixture extracted three times with ethyl acetate
6. dry with materialThe combined organic phases were dried over sodium sulfate
7. concentrationconcentrated
8. customThe residue was purified by column chromatography (eluent: ethyl acetate/cyclohexane 1:2)

ORD record

ord-b22976ef958f497490f349c7c277b25d

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08658698B2