反应详情

Sodium sulfite (643 mg, 5.1 mmol) and NaHCO3 (480 mg, 5.7 mmol) were dissolved in water (20 mL) and 4-amino-3-bromo-5-nitrobenzenesulfonyl chloride ((Example 318: step b) 940 mg, 3 mmol) was added. The suspension was stirred for 1 h at rt and 5 mL of EtOH was added to aid dissolution. The mixture was stirred for 4 h at rt, during which nearly all of the sulfonyl chloride had dissolved and the major spot on TLC was at the baseline. The solvent was removed in vacuo and DMF was added (10 mL). The mixture was stirred for 15 min and the inorganic salts were allowed to settle. The DMF was removed via syringe, the salts were washed with a second portion of DMF (10 mL), and the combined DMF solution was slowly added to a 0° C. solution of 4-bromo-5-nitro-thiophene-2-carboxylic acid methyl ester ((Example 114: step c) 800 mg, 3 mmol) in DMF (20 mL). The solution was stirred for 0° C. for 1 h then overnight at rt. The DMF was removed in vacuo and the residue was partitioned between EtOAc (100 mL) and aq NaHCO3 (30 mL). The layers were separated and the organic layer was washed with aq NaHCO3 (2×20 mL), water (30 mL), and brine (30 mL), then dried over soldium sulfate. The solution was concentrated and the residue was dissolved in THF (20 mL) and cooled to −78° C. A solution of sodium methoxide in methanol (1M, 3.75 mL, 3.75 mmol) was added dropwise and the reaction was stirred for 30 min. Acetic acid (500 μL) was added followed by EtOAc (100 mL). The solution was washed with NaHCO3 (3×30 mL), brine (40 mL), and was dried over sodium sulfate. Concentration and chromatography of the residue yielded the product (430 mg). 1H-NMR (CDCl3): δ 8.88 (d, 1H, J=2.1 Hz), 8.27 (d, 1H, J=2.1 Hz), 8.06 (s, 1H), 3.93 (s, 3H), 2.67 (s, 3H).

1. dissolutionhad dissolved
2. customThe solvent was removed in vacuo and DMF
3. additionwas added (10 mL)
4. stirringThe mixture was stirred for 15 min
5. customThe DMF was removed via syringe
6. washthe salts were washed with a second portion of DMF (10 mL)
7. stirringThe solution was stirred for 0° C. for 1 h
8. customovernight
9. customat rt
10. customThe DMF was removed in vacuo
11. customthe residue was partitioned between EtOAc (100 mL) and aq NaHCO3 (30 mL)
12. customThe layers were separated
13. washthe organic layer was washed with aq NaHCO3 (2×20 mL), water (30 mL), and brine (30 mL)
14. customdried
15. concentrationThe solution was concentrated
16. dissolutionthe residue was dissolved in THF (20 mL)
17. temperaturecooled to −78° C
18. stirringthe reaction was stirred for 30 min
19. washThe solution was washed with NaHCO3 (3×30 mL), brine (40 mL)
20. dry with materialwas dried over sodium sulfate
21. concentrationConcentration and chromatography of the residue