4-氯-2-氟苯甲醚

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:-55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 4-chloro-2-fluoro-1-methoxy-benzene (Aldrich; 10.2 g, 63.5 mmol) in dry tetrahydrofuran (500 mL) was cooled to −78° C. under a nitrogen atmosphere. A solution of lithium diisopropylamide (1.8 M in tetrahydrofuran/heptane/ethylbenzene, 39.9 mL, 70.2 mmol) was added dropwise by syringe. The reaction mixture was warmed to −55° C. and held at this temperature for 1 h. The mixture was then cooled again to −78° C., and dry N,N-dimethylformamide (10.7 mL, 139 mmol) was added by syringe. The cooling bath was removed and the reaction was allowed to warm to −10° C. and quenched by the addition of ice flakes (˜200 mL) and a solution of saturated ammonium chloride (200 mL). Ethyl acetate (200 mL) was added, the layers were separated and the aqueous later was extracted with ethyl acetate (200 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, evaporated, and purified by silica gel chromatography, eluting with 0-30% ethyl acetate/hexanes to give 6-chloro-2-fluoro-3-methoxy-benzaldehyde (5.6 g, 47% yield) as an oil that solidified upon standing. The mixture was then cooled again to −78° C. The cooling bath was removed to warm to −10° C. quenched by the addition of ice flakes (˜200 mL) Ethyl acetate (200 mL) was added the layers were separated the aqueous later was extracted with ethyl acetate (200 mL) The combined organic layers were washed with brine dried over sodium sulfate filtered evaporated purified by silica gel chromatography eluting with 0-30% ethyl acetate/hexanes

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

实验步骤: n-Butyllithium (11.7 ml, 18.77 mmol) was added dropwise to a solution of 4-chloro-2-fluoroanisole (2.01 g, 12.52 mmol) in tetrahydrofuran (20 ml) at −78° C. and the reaction was stirred for 30 mins. Crushed solid carbon dioxide was added in one portion and the reaction was then allowed to warm to room temperature. The solvent was evaporated and the residue dissolved in water. Sodium hydroxide (2M to pH˜14) was added and the aqueous layer extracted with ethyl acetate. The aqueous layer was acidified with hydrochloric acid (5M, pH˜1) and the title compound was collected as a colourless solid (2.25 g, 88%). The compound was dried in vacuo. was added in one portion The solvent was evaporated the residue dissolved in water Sodium hydroxide (2M to pH˜14) was added the aqueous layer extracted with ethyl acetate the title compound was collected as a colourless solid (2.25 g, 88%) The compound was dried in vacuo

反应条件: temp:0.00; pressure:0.00; stir: