Propargyl bromide → HCID 89601091, compound

Participants

Reaction Steps

To a stirred solution of 2-(4-bromo-2-chloro-6-methoxy-phenyl)-3-methoxy-cyclopent-2-en-1-one (0.500 g, 1.51 mmol) in anhydrous tetrahydrofuran (10 mL) under an nitrogen atmosphere at −78°C. was added KHMDS (potassium hexamethyldisilazide) (1.81 mL of a 1.0M solution in tetrahydrofuran, 1.81 mmol) dropwise and the reaction was allowed to stir at this temperature for 55 minutes. Propargyl bromide (80 wt % in toluene, 0.202 mL, 1.81 mmol) was diluted in anhydrous tetrahydrofuran (2.5 mL) under an nitrogen atmosphere and then added dropwise to the reaction mixture. The reaction was stirred at −78°C. for 30 minutes and then allowed to warm to room temperature over 18 hours. The reaction was quenched by addition of saturated aqueous ammonium chloride solution (10 mL) followed by EtOAc (10 mL). Water (1 mL) was added and then the phases were separated and aqueous was extracted with further EtOAc (2×10 ml). The combined organic extracts were washed with brine (10 ml), dried over MgSO4, filtered and evaporated to dryness under reduced pressure to give an orange gum. The crude product was dissolved in dichloromethane, adsorbed onto silica and purified by flash chromatography over silica using a dichloromethane/MeOH gradient to give the desired product (254 mg, 46%) as a yellow gum. 1H NMR (400 MHz, CDCl3) δ ppm 7.23 (s, 1H), 6.95 (s, 1H), 3.78 (s, 3H), 3.66 (s, 3H), 3.14-3.10 (m, 1H), 2.79-2.51 (m, 4H), 2.00 (s, 1H).

Provenance & Evidence