反应详情

To a solution of ethyl 3-(aminomethyl)-6-chloro-2-fluorobenzoate (Intermediate-2, step-1, 800 mg, 3.45 mmol) and 3-hydroxy-2,2-dimethylpropanoic acid (591 mg, 5.00 mmol) in DMF (5 mL) were added (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (2.29 g, 5.18 mmol) and DIPEA (1.29 g, 10.0 mmol). Then reaction mixture was stirred at rt for 12 h and it was diluted with EtOAc, washed with H2O and brine. The organic layer was separated, dried, filtered and concentrated. The residue was purified by column chromatography to afford 700 mg of the title product. 1H NMR (400 MHz, DMSO d6): δ 8.09-8.06 (t, J=8.0 Hz, 1H), 7.45-7.38 (m, 2H), 4.91-4.88 (t, J=5.2 Hz, 1H), 4.42-4.37 (q, J=8.0 Hz, 2H), 4.29-4.28 (d, J=5.6 Hz, 2H), 3.48 (m, 2H), 1.33-1.29 (t, J=8.0 Hz, 3H), 1.05 (s, 6H).

1. customThen reaction mixture
2. washwashed with H2O and brine
3. customThe organic layer was separated
4. customdried
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was purified by column chromatography