β-氯代丁酮

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(6-fluoro-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (60 mg, 0.083 mmol) in DMF (4 mL) was added 4-chlorobutan-2-one (11 mg, 0.1 mmol) followed by K2CO3 (34 mg, 0.25 mmol). The mixture was heated at 65° C. for 1.5 hours. After cooling to room temperature, the mixture was poured into water and filtered to give N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(6-fluoro-1-(3-oxobutyl)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (40 mg, 61%). After drying, the crude was used into the next step without further purification. LCMS: (M+H)+=795. After cooling to room temperature filtered

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(6-fluoro-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (60 mg, 0.083 mmol) in DMF (4 mL) was added 4-chlorobutan-2-one (11 mg, 0.1 mmol) followed by K2CO3 (34 mg, 0.25 mmol). The mixture was heated at 65° C. for 1.5 hours. After cooling to room temperature, the mixture was poured into water and filtered to give N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(6-fluoro-1-(3-oxobutyl)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (40 mg, 61%). After drying, the crude was used into the next step without further purification. LCMS: (M+H)+=795. After cooling to room temperature filtered

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of N-tert-butyl-2-(5-(difluoromethoxy)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (100 mg, 0.156 mmol) in DMF (4 mL) was added 4-chlorobutan-2-one (20 mg, 0.187 mmol) followed by K2CO3 (65 mg, 0.468 mmol). The mixture was heated at 65° C. for 1.5 hours. After cooling to room temperature, the mixture was poured into water, filtered and dried to give N-tert-butyl-2-(5-(difluoromethoxy)-1-(3-oxobutyl)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide. The crude product was used in the next step without purification. MS: (M+H)+=713. After cooling to room temperature filtered dried

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of N-tert-butyl-2-(5-(difluoromethoxy)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (100 mg, 0.156 mmol) in DMF (4 mL) was added 4-chlorobutan-2-one (20 mg, 0.187 mmol) followed by K2CO3 (65 mg, 0.468 mmol). The mixture was heated at 65° C. for 1.5 hours. After cooling to room temperature, the mixture was poured into water, filtered and dried to give N-tert-butyl-2-(5-(difluoromethoxy)-1-(3-oxobutyl)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide. The crude product was used in the next step without purification. MS: (M+H)+=713. After cooling to room temperature filtered dried

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

实验步骤: 3-Hydroxy-chromen-2-one (16.2 g, 100 mmol) is dissolved into 100 mL of anhydrous THF in a three neck flask equipped with a condenser, stir bar, and argon inlet. To the mixture is added 27.6 g (200 mmol) of anhydrous potassium carbonate and 2.0 g of 18-crown-6. 4-Chloro-2-butanone (15.9 g, 150 mmol) is added and the system is refluxed for 16 hours, cooled to room temperature, filtered, and the organic solvents are removed by rotary evaporation. The solid organic residue is purified by column chromatography using 3:1 ethyl acetate:hexanes to yield 3-(3-oxo-butoxy)-chromen-2-one. equipped with a condenser the system is refluxed for 16 hours filtered the organic solvents are removed by rotary evaporation The solid organic residue is purified by column chromatography

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

实验步骤: 3-Hydroxy-chromen-2-one (16.2 g, 100 mmol) is dissolved into 100 mL of anhydrous THF in a three neck flask equipped with a condenser, stir bar, and argon inlet. To the mixture is added 27.6 g (200 mmol) of anhydrous potassium carbonate and 2.0 g of 18-crown-6. 4-Chloro-2-butanone (15.9 g, 150 mmol) is added and the system is refluxed for 16 hours, cooled to room temperature, filtered, and the organic solvents are removed by rotary evaporation. The solid organic residue is purified by column chromatography using 3:1 ethyl acetate:hexanes to yield 3-(3-oxo-butoxy)-chromen-2-one. equipped with a condenser the system is refluxed for 16 hours filtered the organic solvents are removed by rotary evaporation The solid organic residue is purified by column chromatography

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(6-fluoro-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (60 mg, 0.083 mmol) in DMF (4 mL) was added 4-chlorobutan-2-one (11 mg, 0.1 mmol) followed by K2CO3 (34 mg, 0.25 mmol). The mixture was heated at 65° C. for 1.5 hours. After cooling to room temperature, the mixture was poured into water and filtered to give N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(6-fluoro-1-(3-oxobutyl)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (40 mg, 61%). After drying, the crude was used into the next step without further purification. LCMS: (M+H)+=795. After cooling to room temperature filtered

反应条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of N-tert-butyl-2-(5-(difluoromethoxy)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (100 mg, 0.156 mmol) in DMF (4 mL) was added 4-chlorobutan-2-one (20 mg, 0.187 mmol) followed by K2CO3 (65 mg, 0.468 mmol). The mixture was heated at 65° C. for 1.5 hours. After cooling to room temperature, the mixture was poured into water, filtered and dried to give N-tert-butyl-2-(5-(difluoromethoxy)-1-(3-oxobutyl)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide. The crude product was used in the next step without purification. MS: (M+H)+=713. After cooling to room temperature filtered dried

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

实验步骤: A process for the production of 2,3,6-trimethylphenol which comprises reacting a carbonyl compound selected from the group consisting of methyl vinyl ketone, methyl β-hydroxyethyl ketone, methyl β-methoxyethyl ketone, methyl β-phenoxyethyl ketone, methyl β-acetyloxyethyl ketone, methyl β-benzoyloxyethyl ketone, methyl β-methyl-sulfonyloxyethyl ketone, methyl β-phenylsulfonyloxyethyl ketone, methyl β-dimethylaminoethyl ketone, methyl β-chloroethyl ketone, dimethyl-(β-acetylethyl)-sulfonium bromide or trimethyl-(β-acetylethyl)-ammonium iodide to a mixture of diethyl ketone and a basic reagent selected from the group consisting of an alkali metal, an alkaline earth metal, a hydroxide, oxide, alcoholate, amide, hydride or organo metallic compound of an alkali metal or alkaline earth metal, and a quaternary ammonium hydroxide, the amount of said diethyl ketone being in the molar ratio of 1:1 to 50:1 with respect to the total amount of carbonyl compound added, at a reaction temperature of 20° to 150° C. to produce 2,3,6-trimethyl-2-cyclohexen-1-one, and dehydrogenating the latter to produce 2,3,6-trimethylphenol.

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: A process for the production of 2,3,6-trimethylphenol which comprises reacting a carbonyl compound selected from the group consisting of methyl vinyl ketone, methyl β-hydroxyethyl ketone, methyl β-methoxyethyl ketone, methyl β-phenoxyethyl ketone, methyl β-acetyloxyethyl ketone, methyl β-benzoyloxyethyl ketone, methyl β-methyl-sulfonyloxyethyl ketone, methyl β-phenylsulfonyloxyethyl ketone, methyl β-dimethylaminoethyl ketone, methyl β-chloroethyl ketone, dimethyl-(β-acetylethyl)-sulfonium bromide or trimethyl-(β-acetylethyl)-ammonium iodide to a mixture of diethyl ketone and a basic reagent selected from the group consisting of an alkali metal, an alkaline earth metal, a hydroxide, oxide, alcoholate, amide, hydride or organo metallic compound of an alkali metal or alkaline earth metal, and a quaternary ammonium hydroxide, the amount of said diethyl ketone being in the molar ratio of 1:1 to 50:1 with respect to the total amount of carbonyl compound added, at a reaction temperature of 20° to 150° C. to produce 2,3,6-trimethyl-2-cyclohexen-1-one, and dehydrogenating the latter to produce 2,3,6-trimethylphenol.