Ethyl 4-bromobutyrate → Ethyl 4-(2,4-dimethyl-3-nitrophenyl)butanoate

Participants

Reaction Conditions

Reaction Steps

A three-necked flask equipped with a thermometer, a gas inlet, and a magnetic stirring bar was charged under argon with MnBr2 (320 mg, 1.5 mmol) in DMPU (25 ml). CuCl (85 mg, 1 mmol), ethyl 4-bromobutyrate (5.85 g, 30 mmol) and Et2Zn (2.7 ml, 27 mmol) were successively added. The reaction mixture turned dark red and was stirred for 4 h at 25° C. After cooling to −30° C., a solution of Cl2Pd(dppf) (0.925 g, 10 mmol) and 2,4-dimethyl-3-nitroiodobenzene (6.93 g, 25 mmol) in anhydrous THF (25 ml) was slowly added. The reaction mixture was warmed to 25° C. for 30 min and was then stirred at 65° C. overnight and quenched with an aqueous 2N HCl solution (100 ml). This mixture was extracted with CH2Cl2 three times, and the organic layer was dried over anhydrous Na2SO4. The solvent was removed under reduced pressure, and the crude residue obtained was purified by Biotage (hexane/EtOAc, 0-30%, 40 min) to give 4.5 g of yellow oily products (68%). 1H-NMR δ (CDCl3, 300 MHz): 7.13 (d, J=7.8 Hz, 1H), 7.03 (d, J=7.8 Hz, 1H), 4.12 (q, J=7.2 Hz, 2H), 2.64 (t, J=7.8 Hz, 2H), 2.34 (t, J=7.8 Hz, 2H), 2.23 (s, 3H), 2.20 (s, 3H), 1.86 (m, J=7.8 Hz, 2H), 1.24 (t, J=7.8 Hz, 3H).

Provenance & Evidence