Water → 6-Chloro-2-phenyl-4H-3,1-benzoxazin-4-one

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Reaction Steps

Benzoyl chloride (5.3 mL, 45 mmol) was added dropwise to a suspension of Na2CO3 (3.8 g, 36 mmol) and 2-amino-5-chloro-benzoic acid (3.1 g, 18 mmol) in THF (60 mL). The mixture was allowed to stir for 16 h and then H2O (200 mL) was added. The resulting precipitate was collected by filtration, washed with MeOH/H2O (1/1, 100 mL) and then dried in vacuo to provide 6-chloro-2-phenyl-benzo[d][1,3]oxazin-4-one (4.3 g, 92%). To a suspension of the benzoxazinone (5.0 g, 19 mmol) in CH2Cl2 (100 mL) at −78° C. was added o-tolylmagnesium chloride (2 M in THF, 48 mmol) dropwise. The mixture was allowed to warm to −30° C. and stir for 1 h. 1N HCl (100 mL) was then added. The organic phase was collected and the aqueous phase was washed with CH2Cl2 (2×50 mL). The combined organic portions were washed with 0.1N NaOH (2×50 mL), dried over MgSO4, filtered and concentrated in vacuo to provide N-[4-chloro-2-(2-methyl-benzoyl)-phenyl]-benzamide (6.3 g, 93%). The acylated amino-benzophenone (3.5 g, 10 mmol) was dissolved in MeOH (50 mL) containing KOH (3 M, 30 mmol) and was refluxed for 16 h. The solution was then cooled to room temperature and diluted with H2O (50 mL) and EtOAc (100 mL). The organic phase was collected, washed with H2O (3×50 mL), dried over MgSO4, filtered and evaporated to dryness in vacuo to provide 1m (2.4 g, 98%) MS m/z=246 (M+H).

Provenance & Evidence