4-Methoxybenzonitrile → 4-Methoxy-N-methyl-benzamidine

Temperature

0 °C

Methylamine hydrochloride (2.28 g, 33.8 mmol) was suspended in toluene (16 ml). After cooling the resulting mixture to 0° C., trimethylaluminum (2M in toluene) was added drop-wise under Ar, followed by warming the mixture to r.t and stirring for 2 h. To this mixture was then added a solution of 4-methoxybenzonitrile in toluene (16 ml), followed by stirring at 80° C. for 24 h. The reaction mixture was cooled to r.t. and slowly poured in to a slurry of silica gel (10 g) in CHCl3 (75 ml). The slurry was stirred at r.t for 15 minutes and filtered using MeOH. The filtrate was concentrated. The isolated residue was dissolved in water (50 ml) and extracted with CHCl3. The combined organic phase was washed with brine, dried (Na2SO4), filtered and concentrated in-vacuo, to isolate the title compound (1.25 g). 1H-NMR (DMSO-d6): 7.68 (d, 2H), 6.91 (dd, 2H), 6.33 (br. s, 2H), 3.77 (s, 3H), 2.77 (s, 3H)

1. temperatureby warming the mixture
2. stirringby stirring at 80° C. for 24 h
3. temperatureThe reaction mixture was cooled to r.t.
4. stirringThe slurry was stirred at r.t for 15 minutes
5. filtrationfiltered
6. concentrationThe filtrate was concentrated
7. dissolutionThe isolated residue was dissolved in water (50 ml)
8. extractionextracted with CHCl3
9. washThe combined organic phase was washed with brine
10. dry with materialdried (Na2SO4)
11. filtrationfiltered
12. concentrationconcentrated in-vacuo

ORD record

ord-f8a417d31c2644709a48e4667cba736b

Source dataset

uspto-grants-2009_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07585881B2