3-Butyn-1-OL → 4-(4-Chloro-2-methoxy-phenyl)-but-3-yn-1-ol

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 2-bromo-5-chloroanisole (2 g, 9 mmol), Pd(PPh3)4 (520 mg, 0.45 mmol), and CuI (400 mg) in pyrrolidine (20 mL) was added a solution of 3-butyn-1-ol (1.26 g, 18 mmol) in pyrrolidine (30 mL). The reaction mixture was stirred at 80° C. for 6 h, and then concentrated in vacuo. The resulting residue was extracted with ethyl acetate and the organic phase was washed with 1N hydrochloric acid, followed by water, then brine, and dried over sodium sulfate. Upon removal of the solvent under reduced pressure, the crude product was subjected to column chromatography on silica gel (gradient elution with 0%-40% EtOAc/hexane) to give 4-(4-chloro-2-methoxy-phenyl)-but-3-yn-1-ol as a colorless oil (1.46 g, 76.7%). 1H NMR (300 MHz, CDCl3) δ ppm 7.29 (d, J=8.2 Hz, 1H), 6.88 (dd, J=8.2, 1.6 Hz, 1H), 6.85 (d, J=1.6 Hz, 1H), 3.87 (s, 3H), 3.82 (t, J=6.2 Hz, 2H), 2.73 (t, J=6.2 Hz, 2H), 1.92 (br. s, 1H).

Provenance & Evidence