1-(chloromethyl)-2-fluoro-3-methoxybenzene

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: 2-Fluoro-3-methoxybenzyl alcohol from Step 2 (12.16 g, 78 mmol) was dissolved in concentrated hydrochloric acid (60 mL) and hydrochloric acid gas was bubbled through the solution for 3 minutes. The flask was capped and the reaction stirred at room temperature (21 hours). The reaction mixture was extracted with ether, dried over MgSO4 and concentrated in vacuo to give 2-fluoro-3-methoxybenzyl chloride (10.36 g, 76%) as a green oil: 1H NMR (acetone-d6) 300 MHz 7.12 (m, 2H) 7.05 (m, 1H) 4.73 (s, 2H) 3.89 (s, 3H); 19F NMR (acetone-d6) 300 MHz -142.07(m). hydrochloric acid gas was bubbled through the solution for 3 minutes The flask was capped The reaction mixture was extracted with ether dried over MgSO4 concentrated in vacuo

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

実験手順: 2-Fluoro-3-methoxybenzyl alcohol from Step 2 (12.16 g, 78 mmol) was dissolved in concentrated hydrochloric acid (60 mL) and hydrochloric acid gas was bubbled through the solution for 3 minutes. The flask was capped and the reaction stirred at room temperature (21 hours). The reaction mixture was extracted with ether, dried over MgSO4 and concentrated in vacuo to give 2-fluoro-3-methoxybenzyl chloride (10.36 g, 76%) as a green oil: 1H NMR (acetone-d6) 300 MHz 7.12 (m, 2H) 7.05 (m, 1H) 4.73 (s, 2H) 3.89 (s, 3H); 19F NMR (acetone-d6) 300 MHz -142.07(m). hydrochloric acid gas was bubbled through the solution for 3 minutes The flask was capped The reaction mixture was extracted with ether dried over MgSO4 concentrated in vacuo

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

実験手順: 2-Fluoro-3-methoxybenzyl alcohol from Step 2 (12.16 g, 78 mmol) was dissolved in concentrated hydrochloric acid (60 mL) and hydrochloric acid gas was bubbled through the solution for 3 minutes. The flask was capped and the reaction stirred at room temperature (21 hours). The reaction mixture was extracted with ether, dried over MgSO4 and concentrated in vacuo to give 2-fluoro-3-methoxybenzyl chloride (10.36 g, 76%) as a green oil: 1H NMR (acetone-d6) 300 MHz 7.12 (m, 2H) 7.05 (m, 1H) 4.73 (s, 2H) 3.89 (s, 3H); 19F NMR (acetone-d6) 300 MHz -142.07(m). hydrochloric acid gas was bubbled through the solution for 3 minutes The flask was capped The reaction mixture was extracted with ether dried over MgSO4 concentrated in vacuo

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

実験手順: 24.89 g (142.56 mmol) of 2-fluoro-3-methoxybenzyl chloride is stirred in 200 ml of DMSO with 8.38 g (171.07 mmol) of sodium cyanide for three hours at 90° C. The reaction mixture is poured into water and extracted four times with methyl tert-butyl ether. The combined organic phases are washed with brine, dried, the desiccant is suctioned off, and the solvent is spun off. First, only a portion of the residue (21.43 g) is incorporated in crude form into the next stage. extracted four times with methyl tert-butyl ether The combined organic phases are washed with brine dried

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

実験手順: 24.79 g (158.75 mmol) of 2-fluoro-3-methoxybenzyl alcohol is dissolved in 35 ml of dichloromethane. While being cooled slightly, 58.4 ml of thionyl chloride is added in drops, and the batch is then stirred overnight at room temperature. The reaction mixture is spun in until a dry state is reached, the residue is dissolved in methyl tert-butyl ether, and it is shaken twice with semi-saturated potassium carbonate solution. The aqueous phase is extracted once with methyl tert-butyl ether. The combined organic extracts are worked up as usual. The residue that is obtained is incorporated in crude form into the next stage. While being cooled slightly The aqueous phase is extracted once with methyl tert-butyl ether The residue that is obtained

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

実験手順: 2-Fluoro-3-methoxybenzyl alcohol from Step 2 (12.16 g, 78 mmol) was dissolved in concentrated hydrochloric acid (60 mL) and hydrochloric acid gas was bubbled through the solution for 3 minutes. The reaction was stirred at room temperature (21 hours). The reaction mixture was extracted with ether, dried over MgSO4 and concentrated in vacuo to give 2-fluoro-3-methoxybenzyl chloride (10.36 g, 76%) as a green oil: 1H NNR (acetone-d6) 300 MHz 7.12 (m, 2H) 7.05 (m, 1H) 4.73 (s, 2H) 3.89 (s, 3H); 19F NMR (acetone-d6) 300 MHz -142.07(m). hydrochloric acid gas was bubbled through the solution for 3 minutes The reaction mixture was extracted with ether dried over MgSO4 concentrated in vacuo

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

実験手順: 2-Fluoro-3-methoxybenzyl alcohol from Step 2 (12.16 g, 78 mmol) was dissolved in concentrated hydrochloric acid (60 mL) and hydrochloric acid gas was bubbled through the solution for 3 minutes. The flask was capped and the reaction stirred at room temperature (21 hours). The reaction mixture was extracted with ether, dried over MgSO4 and concentrated in vacuo to give 2-fluoro-3-methoxybenzyl chloride (10.36 g, 76%) as a green oil: 1H NMR (acetone-d6) 300 MHz 7.12 (m, 2H) 7.05 (m, 1H) 4.73 (s, 2H) 3.89 (s, 3H); 19F NMR (acetone-d6) 300 MHz -142.07(m). hydrochloric acid gas was bubbled through the solution for 3 minutes The flask was capped The reaction mixture was extracted with ether dried over MgSO4 concentrated in vacuo

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1-(chloromethyl)-2-fluoro-3-methoxybenzene (8.6 g, 49.3 mmol) in ethanol (60 mL) and water (10 mL), sodium cyanide (4.8 g, 98.5 mmol) was added. The resulting solution was heated at 70° C. for 16 h. After cooling to room temperature, the solution was poured into water (200 mL) and extracted with ethyl acetate (2×200 mL). The combined organic layers were washed (brine), dried (Na2SO4), and concentrated in vacuo to give the title compound (6.7 g). 1H NMR (CDCl3): δ 7.13-7.07 (m, 1H), 7.02-6.92 (m, 2H), 3.89 (s, 3H), 3.81 (s, 2H). After cooling to room temperature extracted with ethyl acetate (2×200 mL) The combined organic layers were washed (brine) dried (Na2SO4) concentrated in vacuo

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1-(chloromethyl)-2-fluoro-3-methoxybenzene (8.6 g, 49.3 mmol) in ethanol (60 mL) and water (10 mL), sodium cyanide (4.8 g, 98.5 mmol) was added. The resulting solution was heated at 70° C. for 16 h. After cooling to room temperature, the solution was poured into water (200 mL) and extracted with ethyl acetate (2×200 mL). The combined organic layers were washed (brine), dried (Na2SO4), and concentrated in vacuo to give the title compound (6.7 g). 1H NMR (CDCl3): δ 7.13-7.07 (m, 1H), 7.02-6.92 (m, 2H), 3.89 (s, 3H), 3.81 (s, 2H). After cooling to room temperature extracted with ethyl acetate (2×200 mL) The combined organic layers were washed (brine) dried (Na2SO4) concentrated in vacuo