3-hydroxy-3-methylpentanedinitrile

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

实验步骤: Hydrogen bromide solution (33 wt. % in acetic acid) (17.8 ml, 98.92 mmol) was added dropwise to 3-hydroxy-3-methyl-pentanedinitrile (3.07 g, 24.73 mmol) with stirring. The reaction was stirred overnight at room temperature. Saturated aqueous sodium hydrogencarbonate was added until neutralised. The resulting white precipitate was collected by filtration, washed with water and dried under vacuum to give the desired product. Yield 2.55 g, 55%. LCMS MI: 186.89+188.91, RT: 3.16 min, Method: 2. The reaction was stirred overnight at room temperature The resulting white precipitate was collected by filtration washed with water dried under vacuum

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

实验步骤: 56.4 g of 1,3-dicyano-2-methyl-2-hydroxypropane was added carefully to a 33% solution of hydrogen bromide in glacial acetic acid at ice-bath temperature. The reaction mixture was then stirred for 3 days at ambient temperature. The solvent was removed in vacuo and the residual oil was brought to pH 12 with a 10 molar aqueous solution of sodium hydroxide. This alkaline solution was extracted three times each with 100 ml ethyl acetate. The combined organic layers were dried with magnesium sulphate and the solvent removed in vacuo. 56 g (66%) of 6-amino-2-bromo-4-methylpyridine was obtained as a colourless solid of melting point 99° C. The solvent was removed in vacuo This alkaline solution was extracted three times each with 100 ml ethyl acetate The combined organic layers were dried with magnesium sulphate the solvent removed in vacuo

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 50 g 2-methyl-2-chloromethyloxirane in 23 ml concentrated hydrochloric acid at ice-bath temperature a solution of 27.4 g sodium cyanide in 23 ml hydrochloric acid was added. After stirring for 10 hours at that temperature the reaction mixture was warmed to 40° C. and a solution of 33.8 g potassium cyanide in 50 ml water was added. The resulting mixture was warmed to 50° C. and stirred for 4 hours. After cooling the solution was neutralized and extracted three times with 150 ml ethyl acetate each. The combined organic layers were dried with anhydrous magnesium sulphate. Removal of the solvent afforded 56.4 g (96%) of 1,3-dicyano-2-methyl-2-hydroxypropane. This crude material was sufficiently pure to be submitted directly to the following ring closure. The resulting mixture was warmed to 50° C. stirred for 4 hours After cooling the solution extracted three times with 150 ml ethyl acetate each The combined organic layers were dried with anhydrous magnesium sulphate Removal of the solvent

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 50 g 2-methyl-2-chloromethyloxirane in 23 ml concentrated hydrochloric acid at ice-bath temperature a solution of 27.4 g sodium cyanide in 23 ml hydrochloric acid was added. After stirring for 10 hours at that temperature the reaction mixture was warmed to 40° C. and a solution of 33.8 g potassium cyanide in 50 ml water was added. The resulting mixture was warmed to 50° C. and stirred for 4 hours. After cooling the solution was neutralized and extracted three times with 150 ml ethyl acetate each. The combined organic layers were dried with anhydrous magnesium sulphate. Removal of the solvent afforded 56.4 g (96%) of 1,3-dicyano-2-methyl-2-hydroxypropane. This crude material was sufficiently pure to be submitted directly to the following ring closure. The resulting mixture was warmed to 50° C. stirred for 4 hours After cooling the solution extracted three times with 150 ml ethyl acetate each The combined organic layers were dried with anhydrous magnesium sulphate Removal of the solvent

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

实验步骤: 56.4 g of 1,3-dicyano-2-methyl-2-hydroxypropane was added carefully to a 33% solution of hydrogen bromide in glacial acetic acid at ice-bath temperature. The reaction mixture was then stirred for 3 days at ambient temperature. The solvent was removed in vacuo and the residual oil was brought to pH 12 with a 10 molar aqueous solution of sodium hydroxide. This alkaline solution was extracted three times each with 100 ml ethyl acetate. The combined organic layers were dried with magnesium sulphate and the solvent removed in vacuo. 56 g (66%) of 6-amino-2-bromo-4-methylpyridine was obtained as a colourless solid of melting point 99° C. The solvent was removed in vacuo This alkaline solution was extracted three times each with 100 ml ethyl acetate The combined organic layers were dried with magnesium sulphate the solvent removed in vacuo

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 50 g 2-methyl-2-chloromethyloxirane in 23 ml concentrated hydrochloric acid at ice-bath temperature a solution of 27.4 g sodium cyanide in 23 ml hydrochloric acid was added. After stirring for 10 hours at that temperature the reaction mixture was warmed to 40° C. and a solution of 33.8 g potassium cyanide in 50 ml water was added. The resulting mixture was warmed to 50° C. and stirred for 4 hours. After cooling the solution was neutralized and extracted three times with 150 ml ethyl acetate each. The combined organic layers were dried with anhydrous magnesium sulphate. Removal of the solvent afforded 56.4 g (96%) of 1,3-dicyano-2-methyl-2-hydroxypropane. This crude material was sufficiently pure to be submitted directly to the following ring closure. The resulting mixture was warmed to 50° C. stirred for 4 hours After cooling the solution extracted three times with 150 ml ethyl acetate each The combined organic layers were dried with anhydrous magnesium sulphate Removal of the solvent

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

实验步骤: Hydrogen bromide solution (33 wt. % in acetic acid) (17.8 ml, 98.92 mmol) was added dropwise to 3-hydroxy-3-methyl-pentanedinitrile (3.07 g, 24.73 mmol) with stirring. The reaction was stirred overnight at room temperature. Saturated aqueous sodium hydrogencarbonate was added until neutralised. The resulting white precipitate was collected by filtration, washed with water and dried under vacuum to give the desired product. Yield 2.55 g, 55%. LCMS MI: 186.89+188.91, RT: 3.16 min, Method: 2. The reaction was stirred overnight at room temperature The resulting white precipitate was collected by filtration washed with water dried under vacuum

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

实验步骤: A solution of 12.4 g (0.10 moles) of 3-hydroxy-3-methylglutaronitrile in 107 ml of 1.3 M sodium hydroxide is stirred at room temperature while 17.4 ml (0.20 moles) of 30% hydrogen peroxide is slowly added. After the addition of peroxide, the mixture is heated to boiling and boiling is maintained for 2 hours. Thereafter the mixture is cooled, diluted to 1 liter with water and passed through a 200 ml column of Dowex 2 resin in the formate form. The column is then washed with 1 liter of water. Thereafter the product is eluted with 1 liter of 0.1 N formic acid and the eluate evaporated to dryness to afford 3-hydroxy-3-methylglutaric acid monoamide. is slowly added the mixture is heated boiling is maintained for 2 hours Thereafter the mixture is cooled The column is then washed with 1 liter of water Thereafter the product is eluted with 1 liter of 0.1 N formic acid the eluate evaporated to dryness

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2-methyl-2-chloromethyloxirane (50 g; 0.47 mol) in concentrated hydrochloric acid (23 ml) at ice-bath temperature was added a solution of sodium cyanide (27.4 g; 0.56 mol) in hydrochloric acid (23 ml). After stirring for 10 hours at that temperature, the reaction mixture was warmed to 40° C. and a solution of potassium cyanide (33.8 g; 0.52 mol) in water (50 ml) was added. The reaction mixture was warmed to 50° C. and stirred for 4 hours. After cooling, the mixture was neutralized and extracted 3 times each with ethyl acetate (150 ml). The combined extracts were dried with anhydrous magnesium sulphate. Removal of the solvent in vacuo afforded 1,3-dicyano-2-methyl-2-hydroxypropane (56.4 g; 96%). This compound was added carefully to a 33% wet solution of hydrogen bromide in glacial acetic acid at ice-bath temperature. The reaction mixture was stirred for 3 days at ambient temperature. The solvent was removed in vacuo and the residual oil brought to pH 12 with a 10 molar aqueous solution of sodium hydroxide. The alkaline solution was extracted 3 times each with ethyl acetate (100 ml). The extracts were combined and the solvent removed in vacuo to afford 6-amino-2-bromo-4-methylpyridine (56 g; 66%) as colorless crystals. Melting point 99° C. The reaction mixture was warmed to 50° C. stirred for 4 hours After cooling extracted 3 times each with ethyl acetate (150 ml) The combined extracts were dried with anhydrous magnesium sulphate Removal of the solvent in vacuo

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

实验步骤: Hydrogen bromide solution (33 wt. % in acetic acid) (17.8 ml, 98.92 mmol) was added dropwise to 3-hydroxy-3-methyl-pentanedinitrile (3.07 g, 24.73 mmol) with stirring. The reaction was stirred overnight at room temperature. Saturated aqueous sodium hydrogencarbonate was added until neutralised. The resulting white precipitate was collected by filtration, washed with water and dried under vacuum to give the desired product. Yield 2.55 g, 55%. LCMS MI: 186.89+188.91, RT: 3.16 min, Method: 2. The reaction was stirred overnight at room temperature The resulting white precipitate was collected by filtration washed with water dried under vacuum

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

实验步骤: Hydrogen bromide solution (33 wt. % in acetic acid) (17.8 ml, 98.92 mmol) was added dropwise to 3-hydroxy-3-methyl-pentanedinitrile (3.07 g, 24.73 mmol) with stirring. The reaction was stirred overnight at room temperature. Saturated aqueous sodium hydrogencarbonate was added until neutralised. The resulting white precipitate was collected by filtration, washed with water and dried under vacuum to give the desired product. Yield 2.55 g, 55%. LCMS MI: 186.89+188.91, RT: 3.16 min, Method: 2. The reaction was stirred overnight at room temperature The resulting white precipitate was collected by filtration washed with water dried under vacuum

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

实验步骤: 56.4 g of 1,3-dicyano-2-methyl-2-hydroxypropane was added carefully to a 33% solution of hydrogen bromide in glacial acetic acid at ice-bath temperature. The reaction mixture was then stirred for 3 days at ambient temperature. The solvent was removed in vacuo and the residual oil was brought to pH 12 with a 10 molar aqueous solution of sodium hydroxide. This alkaline solution was extracted three times each with 100 ml ethyl acetate. The combined organic layers were dried with magnesium sulphate and the solvent removed in vacuo. 56 g (66%) of 6-amino-2-bromo-4-methylpyridine was obtained as a colourless solid of melting point 99° C. The solvent was removed in vacuo This alkaline solution was extracted three times each with 100 ml ethyl acetate The combined organic layers were dried with magnesium sulphate the solvent removed in vacuo