7,7,9,9-tetramethyl-1,3,8-triazaspiro[4.5]decane-2,4-dione

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

実験手順: A mixture of 7,7,9,9-tetramethyl-1,3,8-triazaspiro[4.5]decane-2,4-dione (5, 22.2 mmol) and KOH (1.24 g, 22.2 mmol) in EtOH was refluxed for 10 min and bromochloroethane (6.35 g, 44.4 mmol) was added and refluxing continued for additional 6 h. Filtered and concentrated to get the crude chloroethylated product which was used as such for the next step (5.5 g). LCMS—[M+H] m/z 228. was refluxed for 10 min refluxing Filtered concentrated to get the crude chloroethylated product which

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

実験手順: A mixture of 7.7 g of 7,7,9,9-tetramethyl-1,3,8-triazaspiro[4.5]decane-2,4-dione, 2.5 g of ethylene glycol bis(2,3-epoxypropyl)ether and 0.1 g of potassium hydroxide in 80 ml of methanol was refluxed for 11 hours. Insoluble materials were then filtered off and the filtrate was washed with hot methanol. The solution was dried and then the solvent evaporated off. The residue was recrystallised from N,N-dimethylformamide, giving the desired compound in the form of white crystals, melting at 262°-264° C. was refluxed for 11 hours Insoluble materials were then filtered off the filtrate was washed with hot methanol The solution was dried the solvent evaporated off The residue was recrystallised from N,N-dimethylformamide

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

実験手順: A mixture of 12 g of 7,7,9,9-tetramethyl-1,3,8-triazaspiro[4.5]decane-2,4-dione, 7 g of bis[p-(2,3-epoxypropoxy)phenyl]methane and 0.1 g (a catalytic amount) of potassium hydroxide was refluxed for 7 hours in 50 ml of methanol. After completion of the reaction, the methanol was evaporated under reduced pressure from the reaction mixture and the residue was dissolved in chloroform. The solution was then washed successively with a 5% w/w aqueous solution of potassium hydroxide and water and dried over anhydrous magnesium sulphate. The solvent was evaporated off under reduced pressure, leaving a residue which was recrystallised from a mixture of benzene and methanol. The desired Compound No. 179 was obtained in the form of white crystals, melting point 113°-118° C. The compound had an Rf value of 0.42 on thin-layer chromatography on silica gel using a 8:1:1 by volume mixture of ethyl acetate, ethanol and triethylamine as developing solvent. After completion of the reaction the methanol was evaporated under reduced pressure from the reaction mixture the residue was dissolved in chloroform The solution was then washed successively with a 5% w/w aqueous solution of potassium hydroxide and water dried over anhydrous magnesium sulphate The solvent was evaporated off under reduced pressure leaving a residue which was recrystallised from a mixture of benzene and methanol 179 was obtained in the form of white crystals, melting point 113°-118° C

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

実験手順: 40.0 g of 7,7,9,9-tetramethyl-1,3,8-triazaspiro[4.5]decane-2,4-dione, 17.5 g of 2,2-bis[4-(2,3-epoxypropoxy)cyclohexyl]propane and 2.0 g of potassium hydroxide were reacted in 300 ml of methanol, following substantially the same procedure as was described in Example 1. The desired Compound No. 118 was obtained in the form of a white powder, having an Rf value of 0.56 on thin-layer chromatography on silica gel using a 8:1:1:1 by volume mixture of ethyl acetate, benzene, ethanol and triethylamine as developing solvent.

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

実験手順: 24.0 g of 7,7,9,9-tetramethyl-1,3,8-triazaspiro[4.5]decane-2,4-dione, 17.0 g of 2,2-bis[p-(2,3-epoxypropoxy)phenyl]propane and 0.5 g of potassium hydroxide were reacted in 400 ml of 50% v/v aqueous ethanol, following the procedure described in Example 1. The desired Compound No. 1 was obtained in the form of crystals melting at 117°-119° C.

反応条件: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a Parr high-pressure reactor, 15.6 grams (0.1 mol) of 2,2,6,6-tetramethyl-4-piperidone (Aldrich Chemicals Inc.), 13.5 grams (0.2 mol) of 97% potassium cyanide, 43.2 grams (0.45 mol) of ammonium carbonate, 120 mL ethanol, and 120 mL water were mixed. The contents were reacted with stirring at 85° C. for 12 hours, cooled to ambient temperature, and poured into 300 mL of water causing the solid product to precipitate. Impurity salts were washed away with water, and the product was dried. The contents were reacted cooled to ambient temperature to precipitate Impurity salts were washed away with water the product was dried

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

実験手順: A mixture of 7,7,9,9-tetramethyl-1,3,8-triazaspiro[4.5]decane-2,4-dione (5, 22.2 mmol) and KOH (1.24 g, 22.2 mmol) in EtOH was refluxed for 10 min and bromochloroethane (6.35 g, 44.4 mmol) was added and refluxing continued for additional 6 h. Filtered and concentrated to get the crude chloroethylated product which was used as such for the next step (5.5 g). LCMS—[M+H] m/z 228. was refluxed for 10 min refluxing Filtered concentrated to get the crude chloroethylated product which

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

実験手順: A mixture of 7.7 g of 7,7,9,9-tetramethyl-1,3,8-triazaspiro[4.5]decane-2,4-dione, 2.5 g of ethylene glycol bis(2,3-epoxypropyl)ether and 0.1 g of potassium hydroxide in 80 ml of methanol was refluxed for 11 hours. Insoluble materials were then filtered off and the filtrate was washed with hot methanol. The solution was dried and then the solvent evaporated off. The residue was recrystallised from N,N-dimethylformamide, giving the desired compound in the form of white crystals, melting at 262°-264° C. was refluxed for 11 hours Insoluble materials were then filtered off the filtrate was washed with hot methanol The solution was dried the solvent evaporated off The residue was recrystallised from N,N-dimethylformamide

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

実験手順: A mixture of 12 g of 7,7,9,9-tetramethyl-1,3,8-triazaspiro[4.5]decane-2,4-dione, 7 g of bis[p-(2,3-epoxypropoxy)phenyl]methane and 0.1 g (a catalytic amount) of potassium hydroxide was refluxed for 7 hours in 50 ml of methanol. After completion of the reaction, the methanol was evaporated under reduced pressure from the reaction mixture and the residue was dissolved in chloroform. The solution was then washed successively with a 5% w/w aqueous solution of potassium hydroxide and water and dried over anhydrous magnesium sulphate. The solvent was evaporated off under reduced pressure, leaving a residue which was recrystallised from a mixture of benzene and methanol. The desired Compound No. 179 was obtained in the form of white crystals, melting point 113°-118° C. The compound had an Rf value of 0.42 on thin-layer chromatography on silica gel using a 8:1:1 by volume mixture of ethyl acetate, ethanol and triethylamine as developing solvent. After completion of the reaction the methanol was evaporated under reduced pressure from the reaction mixture the residue was dissolved in chloroform The solution was then washed successively with a 5% w/w aqueous solution of potassium hydroxide and water dried over anhydrous magnesium sulphate The solvent was evaporated off under reduced pressure leaving a residue which was recrystallised from a mixture of benzene and methanol 179 was obtained in the form of white crystals, melting point 113°-118° C

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

実験手順: 40.0 g of 7,7,9,9-tetramethyl-1,3,8-triazaspiro[4.5]decane-2,4-dione, 17.5 g of 2,2-bis[4-(2,3-epoxypropoxy)cyclohexyl]propane and 2.0 g of potassium hydroxide were reacted in 300 ml of methanol, following substantially the same procedure as was described in Example 1. The desired Compound No. 118 was obtained in the form of a white powder, having an Rf value of 0.56 on thin-layer chromatography on silica gel using a 8:1:1:1 by volume mixture of ethyl acetate, benzene, ethanol and triethylamine as developing solvent.

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

実験手順: 24.0 g of 7,7,9,9-tetramethyl-1,3,8-triazaspiro[4.5]decane-2,4-dione, 17.0 g of 2,2-bis[p-(2,3-epoxypropoxy)phenyl]propane and 0.5 g of potassium hydroxide were reacted in 400 ml of 50% v/v aqueous ethanol, following the procedure described in Example 1. The desired Compound No. 1 was obtained in the form of crystals melting at 117°-119° C.