[Pb](Cl)Cl.Br[CH2:5]Br.[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([C:14](=O)[CH3:15])=[C:10]([O:17][CH3:18])[C:9]=1[F:19].Cl>C1COCC1.ClCCl.C(OCC)C.[Zn].[Ti](Cl)(Cl)(Cl)Cl>[Cl:7][C:8]1[C:9]([F:19])=[C:10]([O:17][CH3:18])[C:11]([C:14](=[CH2:5])[CH3:15])=[CH:12][CH:13]=1
10 g (68.2 mmol) of 3-chloro-2-fluorophenol in 68 ml of dichloromethane and 7.7 ml (98.5 mmol) of pyridine are admixed dropwise at 0° C. with ml 5.1 ml (71.6 mmol) of acetyl chloride. The mixture is stirred for an hour and 100 ml of 1 M hydrochloric acid are added. The mixture is extracted with dichloromethane and the extracts are washed with water. After drying over sodium sulphate and removal of the solvent in vacuo, 13 g of 3-chloro-2-fluorophenyl acetate are obtained, quantitatively. 13 g (68.2 mmol) of 3-chloro-2-fluorophenyl acetate in 6.9 ml of 1,2-dichlorobenzene are added dropwise with ice cooling to 9.2 g (68.9 mmol) of aluminum trichloride in 6.9 ml of 1,2-dichlorobenzene and the mixture is subsequently stirred at 100° C. for 6 hours. It is cooled, diluted with dichloromethane and poured cautiously onto a mixture of 4 M hydrochloric acid and ice. The phases are separated, extraction is carried out with dichloromethane, and the extracts are washed with saturated sodium chloride solution and dried over sodium sulphate. The crude product is purified by column chromatography on silica gel (hexane/ethyl acetate 10-50%) to give 11.4 g of 1-(4-chloro-3-fluoro-2-hydroxyphenyl)ethan-1-one and 0.74 g of 1-(2-chloro-3-fluoro-4-hydroxyphenyl)ethan-1-one. 11.4 g (60.4 mmol) of 1-(4-chloro-3-fluoro-2-hydroxyphenyl)ethan-1-one are dissolved in 120 ml of acetone, and 15.5 g (112 mmol) of potassium carbonate and 6.9 ml (110 mmol) of methyl iodide are added. The mixture is stirred at 70° C. for 7 hours and the solvent is subsequently removed to a large extent. The residue is poured into water and extracted with methyl tert-butyl ether. The extracts are washed with saturated ammonium chloride solution, dried over sodium sulphate and, following the removal of the solvent in vacuo, give 11.3 g of 1-(4-chloro-3-fluoro-2-methoxyphenyl)ethan-1-one. 27.1 g (415 mmol) of zinc dust and 640 mg (2.3 mmol) of lead(II) chloride are suspended in 400 ml of THF and at room temperature 26 ml (230 mmol) of dibromomethane are added. The mixture is stirred for a further 30 minutes and with ice bath cooling 46.1 ml (46.1 mmol) of a 1 M titanium(IV) chloride solution in dichloromethane are added dropwise. After 30 minutes at 5-10° C. 9.3 g (46.1 mmol) of 1-(4-chloro-3-fluoro-2-methoxyphenyl)ethan-1-one in 92 ml of THF are added dropwise at 5° C. The reaction mixture is stirred at room temperature for a further 15 hours. It is diluted with diethyl ether and poured cautiously onto a mixture of 4 M hydrochloric acid and ice. The phases are separated, extraction is carried out with diethyl ether, the extracts are washed with water and dried over sodium sulphate and the solvent is removed. The crude product is purified by column chromatography on silica gel (hexane/ethyl acetate 10-40%) to give 2.68 g of 3-chloro-2-fluoro-6-(1-methyleneethyl)anisole.
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