1-(5-bromo-2-fluorophenyl)-3-oxabicyclo[3.1.0]hexan-2-one

反応条件: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of (1SR,5RS)-1-(5-bromo-2-fluoro-phenyl)-3-oxa-bicyclo[3.1.0]hexan-2-one (intermediate B5A) (4.6 g, 17 mmol) in dioxane (20 ml) at 23° C. was added ammonia (7 M in MeOH, 40 ml) and the mixture was stirred at 23° C. for 2 days (not complete). Evaporated all volatiles and directly subjected to silica gel chromatography with n-heptane/ethyl acetate to give recovered starting material (0.98 g, 21%) and the title compound as a white solid (3.5 g, 72%). MS (ISP): m/z=287.9 [(M+H)+] and 290.0 [(M+2+H)+]. Evaporated all volatiles to give recovered

反応条件: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of commercially available rhodium(II) octanoate dimer (Rh2(C7H16CO2)4) ([CAS No. 73482-96-9], 160 mg, 1 mol %) in DCM (60 ml) at 45° C. was added a solution of (5-bromo-2-fluoro-phenyl)-diazo-acetic acid allyl ester (intermediate B4A) (6.0 g, 20 mmol) in DCM (2×20 ml) via syringe pump within 16 h. Continued refluxing for 1 h, cooled to 23° C., washed with 1 M aqueous hydrochloric acid (HCl) and sat. aqueous sodium hydrogencarbonate solution (NaHCO3-sol.), dried organic layer over sodium sulfate. Removal of the solvent in vacuum left a green solid, which was purified by silica gel column chromatography with n-heptane/ethyl acetate to give the title compound as a light green solid (4.6 g, 85%) [cf. Adv. Synth. Catal. 2001, 343, 299, for an enantioselective version of this reaction]. Continued refluxing for 1 h washed with 1 M aqueous hydrochloric acid (HCl) and sat. aqueous sodium hydrogencarbonate solution (NaHCO3-sol.), dried organic layer over sodium sulfate Removal of the solvent in vacuum left a green solid, which was purified by silica gel column chromatography with n-heptane/ethyl acetate