Methyl iodide → 5-chloro-6-fluoro-1-methyl-1H-benzo[d][1,3]oxazine-2,4-dione

Participants

Reaction Steps

To a suspension of NaH (49 mg, 1.11 mmol) in DMF (2 ml) at RT was added a solution of 5-chloro-6-fluoro-1H-benzo[d][1,3]oxazine-2,4-dione (synthesized in analogy to a procedure described in EP 59391) (200 mg, 0.93 mmol) in DMF (2 ml). The mixture was stirred at RT for 1 h and then methyl iodide (87 μl, 1.39 mmol) was added. The reaction mixture was then warmed up to RT and stirring was continued overnight. The mixture was quenched with water and extracted with ether. The organic phase was washed with water and brine, dried (MgSO4), filtered, and concentrated in vacuo to give a residue which was purified by flash column chromatography (1:1 ethyl acetate:cyclohexane) to give the desired compound (83 mg, 39%) as a light yellow solid. 1H NMR (CDCl3, 300 MHz): 7.56 (dd, J=9.5, 8.0 Hz, 1H), 7.10 (dd, J=9.5, 4.0 Hz, 1H), 3.59 (s, 3H).

Provenance & Evidence