P-Toluenesulfonamide → methyl (2E)-3-(4-bromophenyl)-2-({[(4-methylphenyl)sulfonyl]amino}methyl)-2-propenoate

Participants

Reaction Steps

To a solution of 390 μL (5.46 mmol) of acetyl chloride in 10 mL of THF at 0° C. was added 1.41 g (5.20 mmol) of methyl 2-[(4-bromophenyl)(hydroxy)methyl]-2-propenoate and 870 μL (6.24 mmol) of TEA in 10 mL THF. After 2 hr at ambient temperature another 870 μL (6.24 mmol) of TEA and 390 μL (5.46 mmol) of acetyl chloride was added and the solution stirred at ambient temperature for an additional 1 hr. EtOAc was added and the organics washed with three 50 mL portions of H2O then 50 mL of brine. The organics were dried over Na2SO4 then concentrated. This residue was then taken up in 25 mL of DMF and 4.35 g (25.4 mmol) of 4-methylbenzenesulfonamide and 3.51 g (25.4 mmol) of K2CO3 were added. The mixture was stirred at 50° C. for 3 hr. To the mixture was added 100 mL of EtOAc which was then washed with three 50 mL portions of water, then brine. The solution was concentrated and the residue purified by silica gel chromatography (120 g of silica gel eluting with 0-40% EtOAc in hexanes over 45 minutes) to give 820 mg (37%) of methyl (2E)-3-(4-bromophenyl)-2-({[(4-methylphenyl)sulfonyl]amino}methyl)-2-propenoate as a beige glass. 1H NMR (400 MHz, CDCl3): δ 7.68-7.66 (m, 3H), 7.52 (d, J=7 Hz, 2H), 7.29-7.25 (m, 4H), 5.51 (t, J =6 Hz, 1H), 3.86 (d, J=6 Hz, 2H), 3.75 (s, 3H), 2.43 (s, 3H). ESI-LCMS m/z 425 (M+H)+.

Provenance & Evidence