Methanol → 4-(3-Bromo-4-fluoro-benzenesulfonyl)-5-methylsulfanyl-thiophene-2-carboxylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

3-Bromo-4-fluoro-benzenesulfonyl chloride ((Example 319: part b) 1.9 g, 6.83 mmol) and sodium bicarbonate (1.15 g, 13.66 mmol) was suspended in 16 mL of water at 70° C. A solution of sodium sulfite (1.64 g, 13 mmol) in 15 mL of water was added in 3 portions over 3 h. The mixture was stirred for 16 h, and the solvent was removed in vacuo. DMF (15 mL) was added, the mixture was stirred for 15 min, and the inorganic salts were then 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) 931 mg, 3.5 mmol) in DMF (15 mL). The solution was stirred for 0° C. for 1 h. 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 sodium sulfate. The solution was concentrated and the residue (1.42 g) was dissolved in THF (20 mL) and cooled to −78° C. A solution of sodium methoxide in methanol (1M, 5 mL, 5 mmol) was added dropwise and the reaction was stirred for 30 min at −78° C. 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 title compound (502 mg, 17%) as a yellow solid. 1H-NMR (CDCl3): δ 8.16 (dd, 1H, J=2.3, 6.3 Hz), 7.94 (s, 1H), 7.91 (ddd, 1H, J=2.6, 4.4, 8.6 Hz), 7.39 (dd, 1H, J=5.3, 8.6 Hz).

Provenance & Evidence