7-bromo-5-fluoro-3,4-dihydro-2H-naphthalen-1-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 7-bromo-5-fluoro-3,4-dihydro-2H-naphthalen-1-one (0.290 g, 1.145 mmol) in methanol (8 mL) and dichloromethane (2 mL) at 0° C. is added sodium borohydride (0.066 g, 1.718 mmol) in one portion. After 2 hours at 0° C., water (30 mL) is added and the volatile organics are removed in vacuo. The resulting mixture is extracted with dichloromethane, dried over magnesium sulfate, filtered, and concentrated to afford 7-bromo-5-fluoro-3,4-dihydro-2H-naphthalen-1-ol, which is used in the next step without further purification. the volatile organics are removed in vacuo The resulting mixture is extracted with dichloromethane dried over magnesium sulfate filtered concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-(4-bromo-2-fluoro-phenyl)-butyric acid (0.625 g, 2.154 mmol) and DMF (0.0084 g, 0.108 mmol) in dichloromethane (10 mL) is added oxalyl chloride (0.558 g, 4.309 mmol). The mixture is stirred for 30 min and concentrated in vacuo at room temperature to give a yellow oil, which is re-dissolved in dichloromethane (20 mL) and added dropwise to aluminum chloride (0.402 g, 3.016 mmol) in dichloromethane (20 mL). The mixture is refluxed for 3.5 hours, and then poured into ice-water. The resulting mixture is extracted twice with diethyl ether. The organic phases are combined, washed with saturated aqueous NaHCO3, dried over MgSO4, filtered through a cotton plug, and concentrated. The resulting residue is purified by silica gel flash chromatography (hexanes-ethyl acetate, 19:1 to 9:1) to afford 7-bromo-5-fluoro-3,4-dihydro-2H-naphthalen-1-one; 1H NMR (400 MHz, CDCl3) δ ppm 2.13-2.19 (m, 2 H), 2.67 (t, J=6.6 Hz, 2 H), 2.90 (t, J=6.2 Hz, 2 H), 7.40 (dd, J=8.5, 1.9 Hz, 1 H), 7.98 (s, 1 H). concentrated in vacuo at room temperature to give a yellow oil, which The mixture is refluxed for 3.5 hours The resulting mixture is extracted twice with diethyl ether washed with saturated aqueous NaHCO3 dried over MgSO4 filtered through a cotton plug concentrated The resulting residue is purified by silica gel flash chromatography (hexanes-ethyl acetate, 19:1 to 9:1)