反应详情

To a solution of methyl 6-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-2,3-difluorobenzoate (5.5 g, 19.2 mmol) in methylene chloride (150 mL) was added trifluoroacetic acid (25 mL, Aldrich). The resulting solution was stirred overnight and then concentrated to an oily residue under reduced pressure. The oil was dissolved in tetrahydrofuran (150 mL) and water (100 mL) and lithium hydroxide (2.3 g, 100 mmol, 5 equiv.) were added. The resulting mixture was rapidly stirred overnight. The next morning the reaction was poured into ethyl acetate and 1.0N HCl was added until the pH is adjusted to 7. The organic layer was washed twice with brine and taken to a residue under reduced pressure to afford 6-amino-2,3-difluorobenzoic acid (3.78 g, 22 mmol) of sufficient purity for use directly in the next transformation. 1H NMR (400 MHz, DMSO-d6) δ ppm 6.51 (ddd, J=9.35, 4.22, 2.20 Hz, 1 H), 7.21-7.31 (m, 1 H), 8.71 (s, 1 H).

1. concentrationconcentrated to an oily residue under reduced pressure
2. dissolutionThe oil was dissolved in tetrahydrofuran (150 mL)
3. waitThe resulting mixture was rapidly stirred overnight
4. additionwas added until the pH
5. washThe organic layer was washed twice with brine