Ethyl Acetoacetate → [4-(4-Methyl-piperazine-1-sulfonyl)phenyl]acetic acid ethyl ester

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Reaction Conditions

Reaction Steps

The title A compound, 1-(4-bromo-benzenesulfonyl)-4-methyl-piperazine (5.00 g, 15.663 mmol), ethyl acetoacetate (2.97 mL, 23.495 mmol), 2-(di-tert-butylphosphino)-2-methyl biphenyl (98 mg, 0.313 mmol), palladium acetate (105 mg, 0.157 mmol) and potassium phosphate (9.97 g, 46.989 mmol) are charged to a flask. Toluene (60 mL) is added. The reaction is heated at 90° C. overnight, then cooled to RT. The reaction mixture is poured onto ethyl acetate and water. The organic layer is dried over anhydrous sodium sulfate, filtered and concentrated to afford a brown oil. This is chromatographed using 0→20% methanol in ethyl acetate to afford [4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-acetic acid ethyl ester as a tan solid which contains ˜8% of the acylated material: LC/MS 327.1 (M+1); 1H NMR (400 MHz, DMSO-D6) δ 1.2 (t, J=7.1 Hz, 3 H) 2.1 (s, 3 H) 2.3 (m, 4 H) 2.9 (d, J=4.3 Hz, 4 H) 3.8 (s, 2 H) 4.1 (q, J=7.1 Hz, 2 H) 7.5 (d, J=8.3 Hz, 2 H) 7.6 (d, 7.7 (m, 2 H). C. 3-Cyclopentyl-2-[4-(4-methyl-piperazine-1-sulfonyl)-phenyl]-propionic Acid Ethyl ester

Provenance & Evidence