Diisopropylethylamine → 7-Fluoroisatoic anhydride

Participants

Reaction Conditions

Reaction Steps

2-Amino-4-fluorobenzoic acid methyl ester. 2-Amino-4fluorobenzoic acid (5.0 g, 32 mmol) was dissolved in DCM (50 mL) and cooled to 0° C. Hünig's base (11 ml, 64 mmol) was added followed by triphosgene (3.8 g, 13 mmol). The reaction mixture was stirred for 5 min then allowed to warm to ambient temperature over 45 min. Water was added to the mixture, which was then extracted with DCM (3×), and the combined organic layers were dried (MgSO4). Filtration and concentration provided 7-fluoro-1H-benzo[d][1,3]oxazine-2,4-dione as a tan solid (3.94 g, 21.8 mmol, 68%), which was taken on directly to the next step. To a solution of 7-fluoro-1H-benzo[d][1,3]oxazine-2,4-dione (3.94 g, 21.8 mmol) in DMF (20 mL) was added dry methanol (8.8 mL, 220 mmol) and DMAP (0.27 g, 2.2 mmol). The mixture was allowed to stand overnight, and was then partitioned between EtOAc and water. The organic layer was washed with water (3×) and dried (MgSO4). Filtration and purification on silica gel (MLPC, hexanes/EtOAc) provided the title methyl ester as a white solid (1.89 g, 11.1 mmol, 51%). HPLC (reversed-phase): RT=8.66 min). 1H NMR (400 MHz, CDCl3): 7.87 (m, 1H), 6.37 (m, 2H), 3.86 (s, 3H).

Provenance & Evidence