Methylamine → 3-Chloro-4-(methylamino)benzonitrile

A solution of 3-chloro-4-fluorobenzonitrile (1.0 g), methylamine (16 mL of a 2 M solution in methanol) and diisopropylethylamine was reacted in the microwave at 120° C. for 15 min. The mixture was then partitioned between ethyl acetate (50 mL) and water (50 mL). The organic layer was washed with brine (30 mL), dried (MgSO4) and reduced in vacuo to give 3-chloro-4-methylamino-benzonitrile. A suspension of 3-chloro-4-methylamino-benzonitrile (900 mg) in 2 M aqueous sodium hydroxide solution (30 mL) was heated at reflux for 3 h. After cooling to room temperature, the solution was acidified with 2 M aqueous hydrochloric acid and the resulting solid collected by filtration and air-dried to give 3-chloro-4-methylamino-benzoic acid. To a solution of 3-chloro-4-methylamino-benzoic acid (860 mg) in DMF (20 mL) was added carbonyl diimidazole (630 mg) and the reaction stirred at room temperature for 1 h. Then, methylamine hydrochloride (262 mg) and triethylamine (1.62 mL) were added and the reaction stirred at room temperature for 16 h. The reaction was partitioned between ethyl acetate (50 mL) and water (50 mL). The organic layer was washed with brine (3×40 mL), dried (MgSO4), reduced in vacuo and purified on silica to give 3-chloro-N-methyl-4-methylamino-benzamide.

1. customThe mixture was then partitioned between ethyl acetate (50 mL) and water (50 mL)
2. washThe organic layer was washed with brine (30 mL)
3. dry with materialdried (MgSO4)

ORD record

ord-a3d01cf982ca4751bae117f2e4a5947a

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07928248B2