2-Chloro-4-fluoroanisole

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

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

Procedure: 17.6 g (0.11 mol) of 2-chloro-4-fluoroanisole was dissolved in a dichloromethane solution of 1N titanium tetrachloride, and 88.3 g (1.10 mol) of methoxymethyl chloride was dropwise added thereto at room temperature, followed by stirring at room temperature for 5 hours. after completion of the reaction, the reaction solution was poured into water, followed by stirring at room temperature for 2 hours, and then the aqueous phase was removed. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off. Then, the obtained residue was purified by silica gel column chromatography to obtain 15.5 g (yield: 68%) of the desired product. was dropwise added at room temperature after completion of the reaction by stirring at room temperature for 2 hours the aqueous phase was removed The organic layer was dried over anhydrous magnesium sulfate the solvent was distilled off Then, the obtained residue was purified by silica gel column chromatography

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

Procedure: 17.6 g (0.11 mol) of 2-chloro-4-fluoroanisole was dissolved in a dichloromethane solution of 1N titanium tetrachloride, and 88.3 g (1.10 mol) of methoxymethyl chloride was dropwise added thereto at room temperature, followed by stirring at room temperature for 5 hours. after completion of the reaction, the reaction solution was poured into water, followed by stirring at room temperature for 2 hours, and then the aqueous phase was removed. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off. Then, the obtained residue was purified by silica gel column chromatography to obtain 15.5 g (yield: 68%) of the desired product. was dropwise added at room temperature after completion of the reaction by stirring at room temperature for 2 hours the aqueous phase was removed The organic layer was dried over anhydrous magnesium sulfate the solvent was distilled off Then, the obtained residue was purified by silica gel column chromatography

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

Procedure: 17.6 g (0.11 mol) of 2-chloro-4-fluoroanisole was dissolved in a dichloromethane solution of 1N titanium tetrachloride, and 88.3 g (1.10 mol) of methoxymethyl chloride was dropwise added thereto at room temperature, followed by stirring at room temperature for 5 hours. After completion of the reaction, the reaction solution was poured into water, followed by stirring at room temperature for 2 hours, and then the aqueous phase was removed The organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off. Then, the obtained residue was purified by silica gel column chromatography to obtain 15.5 g (yield: 68%) of the desired product. was dropwise added at room temperature After completion of the reaction by stirring at room temperature for 2 hours the aqueous phase was removed The organic layer was dried over anhydrous magnesium sulfate the solvent was distilled off Then, the obtained residue was purified by silica gel column chromatography

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

Procedure: 17.6 g (0.11 mol) of 2-chloro-4-fluoroanisole was dissolved in a dichloromethane solution of 1N titanium tetrachloride, and 88.3 g (1.10 mol) of methoxymethyl chloride was dropwise added thereto at room temperature, followed by stirring at room temperature for 5 hours. After completion of the reaction, the reaction solution was poured into water, followed by stirring at room temperature for 2 hours, and then the aqueous phase was removed The organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off. Then, the obtained residue was purified by silica gel column chromatography to obtain 15.5 g (yield: 68%) of the desired product. was dropwise added at room temperature After completion of the reaction by stirring at room temperature for 2 hours the aqueous phase was removed The organic layer was dried over anhydrous magnesium sulfate the solvent was distilled off Then, the obtained residue was purified by silica gel column chromatography

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

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

Procedure: Following the procedure for Intermediate 390.2, 2-chloro-4-fluoro-1-methoxybenzene (1.0 g, 6.3 mmol) afforded 840 mg of Intermediate 392.1 as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 3.91 (s, 3H) 6.90-7.00 (m, 1H) 7.41 (dd, J=9.35, 6.32 Hz, 1H) 10.27 (s, 1H)

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

Procedure: 17.6 g (0.11 mol) of 2-chloro-4-fluoroanisole was dissolved in a dichloromethane solution of 1N titanium tetrachloride, and 88.3 g (1.10 mol) of methoxymethyl chloride was dropwise added thereto at room temperature, followed by stirring at room temperature for 5 hours. After completion of the reaction, the reaction solution was poured into water, followed by stirring at room temperature for 2 hours, and then the aqueous phase was removed. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off. Then, the obtained residue was purified by silica gel column chromatography to obtain 15.5 g (yield: 68%) of the desired product. 1H-NMR (300 MHz, CDCl3) δ value: 3.89(3H,s), 5.00(2H,s), 6.97(1H,d), 7.18(1H,d)ppm. was dropwise added at room temperature After completion of the reaction by stirring at room temperature for 2 hours the aqueous phase was removed The organic layer was dried over anhydrous magnesium sulfate the solvent was distilled off Then, the obtained residue was purified by silica gel column chromatography

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

Procedure: To a solution of 2-chloro-4-fluoroanisole (16.5 g, 100 mmol) in THF (500 mL) cooled at −75° C. was added dropwise a solution of t-BuLi in pentane (1.7 M, 61.8 mL, 105 mmol). The reaction was kept at −75° C. for 15 min, quenched at −75° C. with trimethylchlorosilane (19.0 mL, 150 mmol) and finally poured into a saturated solution of sodium bicarbonate. The organic layer was washed with brine, dried over magnesium sulfate and concentrated. The residue was purified by chromatography on silica gel eluting with 20:1 hexane:diethyl ether to give the title product. The organic layer was washed with brine dried over magnesium sulfate concentrated The residue was purified by chromatography on silica gel eluting with 20:1 hexane

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

Procedure: 17.6 g (0.11 mol) of 2-chloro-4-fluoroanisole was dissolved in a dichloromethane solution of 1N titanium tetrachloride, and 88.3 g (1.10 mol) of methoxymethyl chloride was dropwise added thereto at room temperature, followed by stirring at room temperature for 5 hours. after completion of the reaction, the reaction solution was poured into water, followed by stirring at room temperature for 2 hours, and then the aqueous phase was removed. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off. Then, the obtained residue was purified by silica gel column chromatography to obtain 15.5 g (yield: 68%) of the desired product. was dropwise added at room temperature after completion of the reaction by stirring at room temperature for 2 hours the aqueous phase was removed The organic layer was dried over anhydrous magnesium sulfate the solvent was distilled off Then, the obtained residue was purified by silica gel column chromatography

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

Procedure: 17.6 g (0.11 mol) of 2-chloro-4-fluoroanisole was dissolved in a dichloromethane solution of 1N titanium tetrachloride, and 88.3 g (1.10 mol) of methoxymethyl chloride was dropwise added thereto at room temperature, followed by stirring at room temperature for 5 hours. After completion of the reaction, the reaction solution was poured into water, followed by stirring at room temperature for 2 hours, and then the aqueous phase was removed The organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off. Then, the obtained residue was purified by silica gel column chromatography to obtain 15.5 g (yield: 68%) of the desired product. was dropwise added at room temperature After completion of the reaction by stirring at room temperature for 2 hours the aqueous phase was removed The organic layer was dried over anhydrous magnesium sulfate the solvent was distilled off Then, the obtained residue was purified by silica gel column chromatography