2,6-二氟-α-甲基苯甲醇

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

实验步骤: 10 g (63 millimoles) of 1-(2,6-difluorophenyl)ethanol are dissolved in 150 ml of hydrazoic acid (1.2N in toluene). To this solution are added 22.8 g (200 millimoles) of trifluoroacetic acid and the reaction mixture is allowed to stand for 24 hours at room temperature. After dilution with 300 ml of hexane, the reaction solution is washed first with water, then with sodium bicarbonate solution until free of acid and dried over sodium sulfate. The solvent is subsequently removed at 40°-50° C. under reduced pressure. The residue is dissolved in 100 ml of hexane and the solution is filtered through 50 g of silica gel and concentrated by evaporation once more, affording 1-(2,6-difluorophenyl)ethyl azide as a colourless oil. After dilution with 300 ml of hexane, the reaction solution is washed first with water with sodium bicarbonate solution until free of acid and dried over sodium sulfate The solvent is subsequently removed at 40°-50° C. under reduced pressure The residue is dissolved in 100 ml of hexane the solution is filtered through 50 g of silica gel concentrated by evaporation once more

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

实验步骤: 10 g (63 millimoles) of 1-(2,6-difluorophenyl)ethanol are dissolved in 150 ml of hydrazoic acid (1.2N in toluene). To this solution are added 22.8 g (200 millimoles) of trifluoroacetic acid and the reaction mixture is allowed to stand for 24 hours at room temperature. After dilution with 300 ml of hexane, the reaction solution is washed first with water, then with sodium bicarbonate solution until free of acid and dried over sodium sulfate. The solvent is subsequently removed at 40°-50° C. under reduced pressure. The residue is dissolved in 100 ml of hexane and the solution is filtered through 50 g of silica gel and concentrated by evaporation once more, affording 1-(2,6-difluorophenyl)ethyl azide as a colourless oil. After dilution with 300 ml of hexane, the reaction solution is washed first with water with sodium bicarbonate solution until free of acid and dried over sodium sulfate The solvent is subsequently removed at 40°-50° C. under reduced pressure The residue is dissolved in 100 ml of hexane the solution is filtered through 50 g of silica gel concentrated by evaporation once more

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

实验步骤: 10 g (63 millimoles) of 1-(2,6-difluorophenyl)ethanol are dissolved in 150 ml of hydrazoic acid (1.2N in toluene). To this solution are added 22.8 g (200 millimoles) of trifluoroacetic acid and the reaction mixture is allowed to stand for 24 hours at room temperature. After dilution with 300 ml of hexane, the reaction solution is washed first with water, then with sodium bicarbonate solution until free of acid and dried over sodium sulfate. The solvent is subsequently removed at 40°-50° C. under reduced pressure. The residue is dissolved in 100 ml of hexane and the solution is filtered through 50 g of silica gel and concentrated by evaporation once more, affording 1-(2,6-difluorophenyl)ethyl azide as a colourless oil. After dilution with 300 ml of hexane, the reaction solution is washed first with water with sodium bicarbonate solution until free of acid and dried over sodium sulfate The solvent is subsequently removed at 40°-50° C. under reduced pressure The residue is dissolved in 100 ml of hexane the solution is filtered through 50 g of silica gel concentrated by evaporation once more

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

实验步骤: 5.50 g (23.5 mmol) of ethyl 8-hydroxy-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylate Example 239A, 4.46 g (28.2 mmol) of 1-(2,6-difluorophenyl)ethanol, 5.35 ml (27.0 mmol) of diisopropyl azodicarboxylate and 7.08 g (27.0 mmol) of triphenylphosphine were dissolved in 141 ml of THF and stirred at RT for 2 h. 0.70 ml (3.5 mmol) of diisopropyl azodicarboxylate and 0.62 g (2.3 mmol) of triphenylphosphine were added to the reaction mixture, and the reaction solution was stirred at RT for 1 h. The precipitated solid was filtered off and dried under high vacuum. This gave 4.6 g (52.8% of theory; purity 100%) of the title compound. The filtrate was concentrated and purified twice by silica gel chromatography (cyclohexane:ethyl acetate gradient=from 8:1 to 4:1). All product-containing fractions were re-purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA). This gave another 2.16 g (25% of theory) of the target compound. the reaction solution was stirred at RT for 1 h The precipitated solid was filtered off dried under high vacuum The filtrate was concentrated purified twice by silica gel chromatography (cyclohexane:ethyl acetate gradient=from 8:1 to 4:1) All product-containing fractions were re-purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA) This gave another 2.16 g (25% of theory) of the target compound

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

实验步骤: 5.50 g (23.5 mmol) of ethyl 8-hydroxy-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylate Example 239A, 4.46 g (28.2 mmol) of 1-(2,6-difluorophenyl)ethanol, 5.35 ml (27.0 mmol) of diisopropyl azodicarboxylate and 7.08 g (27.0 mmol) of triphenylphosphine were dissolved in 141 ml of THF and stirred at RT for 2 h. 0.70 ml (3.5 mmol) of diisopropyl azodicarboxylate and 0.62 g (2.3 mmol) of triphenylphosphine were added to the reaction mixture, and the reaction solution was stirred at RT for 1 h. The precipitated solid was filtered off and dried under high vacuum. This gave 4.6 g (52.8% of theory; purity 100%) of the title compound. The filtrate was concentrated and purified twice by silica gel chromatography (cyclohexane:ethyl acetate gradient=from 8:1 to 4:1). All product-containing fractions were re-purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA). This gave another 2.16 g (25% of theory) of the target compound. the reaction solution was stirred at RT for 1 h The precipitated solid was filtered off dried under high vacuum The filtrate was concentrated purified twice by silica gel chromatography (cyclohexane:ethyl acetate gradient=from 8:1 to 4:1) All product-containing fractions were re-purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA) This gave another 2.16 g (25% of theory) of the target compound

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

实验步骤: To a cold (ice water) suspension of sodium hydride (409 mg; 10 mmol) in anhydrous DMF (4 mL) is added a solution of 2,6-difluoro-alpha-methylbenzyl alcohol (1.63 g; 10 mmol) in anhydrous DMF (5 mL) over 10 minutes. After allowing to room temperature over 1 hour, this solution is added to a cold (ice water) stirred solution of 2,6-difluorobenzonitrile (1.53 g; 11 mmol) in anhydrous DMF (6 mL), and allowed to room temperature over 2.5 hours. The reaction mixture is poured into ice water with vigorous stirring and the resulting solid is filtered, washed with water, and dried under vacuum at 40° C. overnight to give 1.92 grams of 2-[1-(2,6-difluorophenyl)-ethoxy]-6-fluorobenzonitrile. allowed to room temperature over 2.5 hours the resulting solid is filtered washed with water dried under vacuum at 40° C. overnight

反应条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 2,6-Difluoro-alpha-methylbenzyl alcohol of (B) (14.9 g, 0.094 mol) is dissolved in chloroform (50 ml) and warmed to 60° C. Thionyl chloride (22.4 g, 0.19 mol) is now added dropwise. The whole is kept at 60° C. for 4 hours then stirred overnight at room temperature. Excess thionyl chloride and chloroform are then removed on a rotary evaporator, resulting in pure title product (16.6 g, 99.8%). Excess thionyl chloride and chloroform are then removed on a rotary evaporator

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

实验步骤: 2,6-Difluoroacetophenone of (A) (17.2 g, 0.11 mol) is dissolved in isopropyl alcohol (50 ml) and NaBH4 (2.0 g, 0.055 mol) is added. The resultant mixture is warmed to 60° C. for about 14 hours. A solution of NaOH (4.9 g, 0.12 mol) in water (20 ml) is then added. After 1 hour at 60° C., this reaction mixture is cooled and acidified with dilute HCl. Extraction with methylene chloride provided pure title product (14.9 g, 85.5%). this reaction mixture is cooled Extraction with methylene chloride provided pure title product (14.9 g, 85.5%)

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

实验步骤: 5.50 g (23.5 mmol) of ethyl 8-hydroxy-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylate Example 87A, 4.46 g (28.2 mmol) of 1-(2,6-difluorophenyl)ethanol, 5.35 ml (27.0 mmol) of diisopropyl azodicarboxylate and 7.08 g (27.0 mmol) of triphenylphosphine were dissolved in 141 ml of THF, and the mixture was stirred at RT for 2 h. 0.70 ml (3.5 mmol) of diisopropyl azodicarboxylate and 0.62 g (2.3 mmol) of triphenylphosphine were added to the reaction mixture, and the reaction solution was stirred at RT for 1 h. The precipitated solid was filtered off and dried under high vacuum. This gave 4.6 g (52.8% of theory; purity 100%) of the title compound. The filtrate was concentrated and purified twice by silica gel chromatography (cyclohexane:ethyl acetate gradient=from 8:1 to 4:1). All product-containing fractions were re-purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA). This gave another 2.16 g (25% of theory) of the target compound. the reaction solution was stirred at RT for 1 h The precipitated solid was filtered off dried under high vacuum The filtrate was concentrated purified twice by silica gel chromatography (cyclohexane:ethyl acetate gradient=from 8:1 to 4:1) All product-containing fractions were re-purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA) This gave another 2.16 g (25% of theory) of the target compound

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

实验步骤: 5.50 g (23.5 mmol) of ethyl 8-hydroxy-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylate Example 87A, 4.46 g (28.2 mmol) of 1-(2,6-difluorophenyl)ethanol, 5.35 ml (27.0 mmol) of diisopropyl azodicarboxylate and 7.08 g (27.0 mmol) of triphenylphosphine were dissolved in 141 ml of THF, and the mixture was stirred at RT for 2 h. 0.70 ml (3.5 mmol) of diisopropyl azodicarboxylate and 0.62 g (2.3 mmol) of triphenylphosphine were added to the reaction mixture, and the reaction solution was stirred at RT for 1 h. The precipitated solid was filtered off and dried under high vacuum. This gave 4.6 g (52.8% of theory; purity 100%) of the title compound. The filtrate was concentrated and purified twice by silica gel chromatography (cyclohexane:ethyl acetate gradient=from 8:1 to 4:1). All product-containing fractions were re-purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA). This gave another 2.16 g (25% of theory) of the target compound. the reaction solution was stirred at RT for 1 h The precipitated solid was filtered off dried under high vacuum The filtrate was concentrated purified twice by silica gel chromatography (cyclohexane:ethyl acetate gradient=from 8:1 to 4:1) All product-containing fractions were re-purified by preparative HPLC (RP18 column, mobile phase: acetonitrile/water gradient with addition of 0.1% TFA) This gave another 2.16 g (25% of theory) of the target compound

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

实验步骤: To a cold (ice water) suspension of sodium hydride (409 mg; 10 mmol) in anhydrous DMF (4 mL) is added a solution of 2,6-difluoro-alpha-methylbenzyl alcohol (1.63 g; 10 mmol) in anhydrous DMF (5 mL) over 10 minutes. After allowing to room temperature over 1 hour, this solution is added to a cold (ice water) stirred solution of 2,6-difluorobenzonitrile (1.53 g; 11 mmol) in anhydrous DMF (6 mL), and allowed to room temperature over 2.5 hours. The reaction mixture is poured into ice water with vigorous stirring and the resulting solid is filtered, washed with water, and dried under vacuum at 40° C. overnight to give 1.92 grams of 2-[1-(2,6-difluorophenyl)-ethoxy]-6-fluorobenzonitrile. allowed to room temperature over 2.5 hours the resulting solid is filtered washed with water dried under vacuum at 40° C. overnight

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

实验步骤: 10 g (63 millimoles) of 1-(2,6-difluorophenyl)ethanol are dissolved in 150 ml of hydrazoic acid (1.2N in toluene). To this solution are added 22.8 g (200 millimoles) of trifluoroacetic acid and the reaction mixture is allowed to stand for 24 hours at room temperature. After dilution with 300 ml of hexane, the reaction solution is washed first with water, then with sodium bicarbonate solution until free of acid and dried over sodium sulfate. The solvent is subsequently removed at 40°-50° C. under reduced pressure. The residue is dissolved in 100 ml of hexane and the solution is filtered through 50 g of silica gel and concentrated by evaporation once more, affording 1-(2,6-difluorophenyl)ethyl azide as a colourless oil. After dilution with 300 ml of hexane, the reaction solution is washed first with water with sodium bicarbonate solution until free of acid and dried over sodium sulfate The solvent is subsequently removed at 40°-50° C. under reduced pressure The residue is dissolved in 100 ml of hexane the solution is filtered through 50 g of silica gel concentrated by evaporation once more