Isatoic Anhydride → 2-amino-N-methoxy-N-methylbenzamide

N,O-Dimethylhydroxylamine (102.5 g) was dissolved in 90% ethanol (40 ml). To the solution were added triethylamine (106 g) and isatoic anhydride (74 g). The mixture was heated for 1.5 hour under reflux. The reaction mixture was concentrated, to which was added a saturated aqueous saline solution, followed by extraction with ethyl acetate (500 ml). The organic layer was washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off to leave N-methyl-N-methyloxy-2-aminobenzamide (81 g) as a yellow oily product. This compound (6.8 g) and 1-[(tert-butoxycarbonylamino-1-methyl)ethyl]-3-bromobenzene (10 g) were dissolved in tetrahydrofuran (200 ml). The solution was cooled to −80° C. or below, to which was added dropwise, while stirring, n-butyl lithium (1.6 mol/L) (128 ml) over 1.5 hour. To the reaction mixture was added water (200 ml), which was subjected to extraction with ethyl acetate (300 ml). The organic layer was washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was purified by means of a silica gel column chromatography to give 2-amino-3′-(1-tert-butoxycarbonylamino-1-methyl)ethyl-benzophenone (2.2 g) as a yellow oily product.

1. temperatureThe mixture was heated for 1.5 hour
2. temperatureunder reflux
3. concentrationThe reaction mixture was concentrated, to which
4. additionwas added a saturated aqueous saline solution
5. extractionfollowed by extraction with ethyl acetate (500 ml)
6. washThe organic layer was washed with water
7. dry with materialdried over anhydrous sodium sulfate
8. distillationThe solvent was distilled off

ORD record

ord-3458ca52b5ab4c21a624e1fb78c53500

Source dataset

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06352982B1