反应详情

To a solution of 2-nitro-4-chlorobenzoic acid (5.09, 25.2 mmol) in DCM (100 mL) was added oxalyl chloride (16.8 mL, 34 mmol, 2M in DCM) and DMF (5 drops). The solution was stirred for 1 h and then concentrated by rotary evaporation. The resulting acid chloride was dissolved in DCM. To a solution of 4-(2,2-diethoxyethoxy)-3-methoxyaniline (5.36 g, 21 mmol), triethylamine (4.2 g) and DMAP (0.48 g) in DCM at 0° C. was added the acid chloride solution in 4 portions over 15 min. The reaction was stirred for 18 h and the ice was allowed to melt. The solvents were removed by rotary evaporation and the residue partitioned between water and ethyl acetate. The organic layer was washed with brine, dried and concentrated. The product was purified by by silica gel column chromatography affording the intermediate as a yellow solid (7.91 g, 86%). 1H NMR (DMSO-D6): δ 1.18 (6H, t, J=6.9 Hz), 3.57 (2H, q, J=12.1 Hz), 3.67 (2H, q, J=12.2 Hz), 3.75 (s, 3H), 3.91 (2H, d, J=5.1 Hz), 4.79 (1H, t, J=5.1 Hz), 7.00 (1H, m), 7.18 (1H, d), 7.34 (1H, s), 7.82 (1H, d), 7.95 (1H, d), 8.26 (1H, s), 10.57 (1H, d). LCMS m/z=461 (m+Na+).

1. concentrationconcentrated by rotary evaporation
2. dissolutionThe resulting acid chloride was dissolved in DCM
3. stirringThe reaction was stirred for 18 h
4. customThe solvents were removed by rotary evaporation
5. customthe residue partitioned between water and ethyl acetate
6. washThe organic layer was washed with brine
7. customdried
8. concentrationconcentrated
9. customThe product was purified by by silica gel column chromatography