Butyl bromide → 4-amino-N-[(4-benzyl-2-morpholinyl)methyl]-2-butoxy-5-chlorobenzamide

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 4-amino-N-[(4-benzyl-2-morpholinyl)methyl]-5-chloro-2-hydroxybenzamide (4.0 g) in 1N aqueous sodium hydroxide solution (32 ml), tetrabutylammonium bromide (3.4 g) and a solution of butyl bromide (4.3 g) in dichloromethane (32 ml) are added. The reaction mixture is stirred at 25° C. for 15 hours and concentrated under reduced pressure. To the residue is added ethyl acetate. The organic layer is washed successively with water and saturated aqueous sodium chloride solution, dried over magnesium sulfate, and evaporated under reduced pressure. The residue is chromatographed on silica gel with methanol-chloroform (5:95) to give the title compound (5.5 g) as an oil. The free base thus obtained is dissolved in hot ethanol (20 ml), and fumaric acid (1.5 g) is added. The solution is stirred for some time. The precipitate is collected and recrystallized from ethanol to give the fumarate hemihydrate (4.6 g) of the title compound, mp 188°-190° C.

Provenance & Evidence