3,5-二氟苯-1,2-二醇

反应条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 3,5-Difluorobenzene-1,2-diol (10 g, 69 mmol) was dissolved in dry N,N-dimethylformamide (100 mL), treated with cesium carbonate (56 g, 170 mmol) and stirred for 30 min at 20° C. Bromochloromethane (12 g, 90 mmol) was added and the mixture was heated and stirred at 60° C. for 19 h. After cooling, the mixture was shaken with water (100 mL) and diethyl ether (100 mL). The aqueous phase was extracted again with ether (50 mL). The combined extracts were washed with water (2×20 mL), washed with saturated NaCl (1×10 mL) and dried (Na2SO4). The bulk of the ether was removed by atmospheric distillation through a 300 mm Vigreux column. The pressure was reduced to 75 mmHg and the product was distilled at 70-90° C. to give the title compound as a thick oil (3.0 g, 28%): 1H NMR (400 MHz, CDCl3) δ 6.45 (m, 1H), 6.42 (d, J=2.4 Hz, 1H), 6.39 (d, J=2.4 Hz, 1H), 6.02 (s, 2H); 19F NMR (376 MHz, CDCl3) δ −117.99, −135.90; EIMS m/z 158. the mixture was heated stirred at 60° C. for 19 h After cooling The aqueous phase was extracted again with ether (50 mL) The combined extracts were washed with water (2×20 mL) washed with saturated NaCl (1×10 mL) dried (Na2SO4) The bulk of the ether was removed by atmospheric distillation through a 300 mm Vigreux column the product was distilled at 70-90° C.

反应条件: temp:7.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 3,5-Difluorobenzene-1,2-diol (670 mg, 4.6 mmol) was stirred in dry chloroform (8 mL), treated with thiophosgene (580 mg, 5.0 mmol), cooled to 5-10° C., and treated dropwise with 10% NaOH solution (4.2 g, 11 mmol) over 45 min. After 30 min, the volatiles were removed by rotary evaporation and the residual solid was collected by filtration and washed with water. The solid was dissolved in ethyl acetate (30 mL), washed with water (2×20 mL), washed with saturated NaCl (1×10 mL), dried (Na2SO4), and evaporated. The residue was purified by chromatography on silica with a 0-20% ethyl acetate-hexane gradient to give the title compound (710 mg, 82%): 1H NMR (400 MHz, CDCl3) δ 6.95 (ddd, J=6.8, 2.3, 1.4 Hz, 1H), 6.89 (td, J=9.5, 2.3 Hz, 1H); 19F NMR (376 MHz, CDCl3) δ −109.99 (s), −127.93 (s); EIMS m/z 188. the volatiles were removed by rotary evaporation the residual solid was collected by filtration washed with water The solid was dissolved in ethyl acetate (30 mL) washed with water (2×20 mL) washed with saturated NaCl (1×10 mL) dried (Na2SO4) evaporated The residue was purified by chromatography on silica with a 0-20% ethyl acetate-hexane gradient

反应条件: temp:-25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 3,5-Difluoro-2-methoxyphenol (1.0 g, 6.3 mmol, prepared as described in Jones, Lyn H.; Randall, Amy; Barba, Oscar; Selby, Matthew D., Organic & Biomolecular Chemistry 2007, 5, 3431-3433) was dissolved in dry dichloromethane (11 mL), cooled to −20 to −30° C. and treated in portions with boron tribromide (BBr3) solution in dichloromethane (1.0 M; 13 mL, 13 mmol). The cooling bath was removed and the mixture was stirred for 20 h at 20° C. The mixture was cooled to −30° C., treated in portions with water (3 mL) and then warmed to 20° C. 6 M HCl (10 mL) and ethyl acetate (30 mL) were added, and the mixture was stirred for 20 min to produce two clear phases. The aqueous phase was extracted with ethyl acetate (20 mL), and the combined organic phases were washed with saturated NaCl (10 mL), dried (Na2SO4) and rotary evaporated to give the title compound as an oil which solidified upon standing (720 mg, 78%): 1H NMR (400 MHz, CDCl3) δ 6.51 (ddd, J=9.5, 2.8, 2.1 Hz, 1H), 6.45 (ddd, J=10.3, 8.7, 2.9 Hz, 1H), 5.71 (s, 1H), 5.06 (s, 1H); 19F NMR (376 MHz, CDCl3) δ −119.56, −136.16; EIMS m/z 146. The cooling bath was removed The mixture was cooled to −30° C. treated in portions with water (3 mL) warmed to 20° C 6 M HCl (10 mL) and ethyl acetate (30 mL) were added the mixture was stirred for 20 min to produce two clear phases The aqueous phase was extracted with ethyl acetate (20 mL) the combined organic phases were washed with saturated NaCl (10 mL) dried (Na2SO4) rotary evaporated