3-氨基-2,2,4,4-四甲基硫杂环丁烷

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:175.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Formamide (4.0 g, 89 mmol), 2,2,4,4-tetramethyl-3-oxothietane (1.0 g, 6933 mmol) and boric acid (100 mg) were combined in a Teflon lined Parr bomb which was heated for 15 hours in a 175° C. oil bath. The reaction was cooled and the light brown mixture taken up in water (40 ml). The aqueous solution was extracted with methylene chloride (4×20 ml) and the combined extracts dried (MgSO4) and evaporated under reduced pressure to a light brown oil (1.02 g). The residue was hydrolyzed and the hydrolyzate worked up according to the procedure of Example 1 to give the title product 650 mg (65%), verified by its 1H-NMR spectrum. The reaction was cooled The aqueous solution was extracted with methylene chloride (4×20 ml) the combined extracts dried (MgSO4) evaporated under reduced pressure to a light brown oil (1.02 g)

反应条件: temp:170.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Formamide (8.0 g, 178 mmol), 2,2,4,4-tetramethyl-3-oxothietane (1.0 g, 6.933 mmol) and aluminum chloride hexahydrate (100 mg) were placed in a Teflon lined Parr bomb and heated at 170° C. for 18 hours. The reaction was then cooled and taken up in water (20 ml). The aqueous solution was extracted with methylene chloride (3×20 ml), the extracts combined and concentrated under reduced pressure. The residue was refluxed with 1N HCl (20 ml) for 4 hours, the reaction cooled and washed with methylene chloride (2×20 ml). It was then brought to pH 14 by addition of 6N sodium hydroxide and extracted with the methylene chloride (3×20 ml). The combined extracts were dried (Na2SO4) and concentrated to give 0.600 g (60%) of title product, verified by its 1H-NMR spectrum. The reaction was then cooled The aqueous solution was extracted with methylene chloride (3×20 ml) concentrated under reduced pressure The residue was refluxed with 1N HCl (20 ml) for 4 hours the reaction cooled washed with methylene chloride (2×20 ml) It was then brought to pH 14 by addition of 6N sodium hydroxide extracted with the methylene chloride (3×20 ml) The combined extracts were dried (Na2SO4) concentrated

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

实验步骤: A solution of 14.53 g. (0.1 mole) 3-amino-2,2,4,4-tetramethylthietane and 64.17 g. (0.3 mole) sodium m-periodate in 500 ml. water was stirred overnight at room temperature. The reaction mixture was adjusted to pH 13 with sodium hydroxide solution and the precipitated sodium iodate removed by filtration. The filtrate was washed with 100 ml. ethyl ether, the aqueous phase extracted continuously with methylene chloride over 18 hours, the extract dried (MgSO4) and solvent evaporated in vacuo. The residual solid was recrystallized from ethyl acetate to provide 8.5 g. of product, M.P. 104°-106.5° C. A second crop of crystals was obtained, 2.7 g., M.P. 103°-106° C. Total yield, 63%. the precipitated sodium iodate removed by filtration The filtrate was washed with 100 ml ethyl ether, the aqueous phase extracted continuously with methylene chloride over 18 hours the extract dried (MgSO4) and solvent evaporated in vacuo The residual solid was recrystallized from ethyl acetate to provide 8.5 g A second crop of crystals was obtained

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

实验步骤: A solution of 14.53 g. (0.1 mole) 3-amino-2,2,4,4-tetramethylthietane and 64.17 g. (0.3 mole) sodium m-periodate in 500 ml. water was stirred overnight at room temperature. The reaction mixture was adjusted to pH 13 with sodium hydroxide solution and the precipitated sodium iodate removed by filtration. The filtrate was washed with 100 ml. ethyl ether, the aqueous phase extracted continuously with methylene chloride over 18 hours, the extract dried (MgSO4) and solvent evaporated in vacuo. The residual solid was recrystallized from ethyl acetate to provide 8.5 g. of product, M.P. 104°-106.5° C. A second crop of crystals was obtained, 2.7 g., M.P. 103°-106° C. Total yield, 63%. the precipitated sodium iodate removed by filtration The filtrate was washed with 100 ml ethyl ether, the aqueous phase extracted continuously with methylene chloride over 18 hours the extract dried (MgSO4) and solvent evaporated in vacuo The residual solid was recrystallized from ethyl acetate to provide 8.5 g A second crop of crystals was obtained

反应条件: temp:175.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Formamide (4.0 g, 89 mmol), 2,2,4,4-tetramethyl-3-oxothietane (1.0 g, 6933 mmol) and boric acid (100 mg) were combined in a Teflon lined Parr bomb which was heated for 15 hours in a 175° C. oil bath. The reaction was cooled and the light brown mixture taken up in water (40 ml). The aqueous solution was extracted with methylene chloride (4×20 ml) and the combined extracts dried (MgSO4) and evaporated under reduced pressure to a light brown oil (1.02 g). The residue was hydrolyzed and the hydrolyzate worked up according to the procedure of Example 1 to give the title product 650 mg (65%), verified by its 1H-NMR spectrum. The reaction was cooled The aqueous solution was extracted with methylene chloride (4×20 ml) the combined extracts dried (MgSO4) evaporated under reduced pressure to a light brown oil (1.02 g)

反应条件: temp:170.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Formamide (8.0 g, 178 mmol), 2,2,4,4-tetramethyl-3-oxothietane (1.0 g, 6.933 mmol) and aluminum chloride hexahydrate (100 mg) were placed in a Teflon lined Parr bomb and heated at 170° C. for 18 hours. The reaction was then cooled and taken up in water (20 ml). The aqueous solution was extracted with methylene chloride (3×20 ml), the extracts combined and concentrated under reduced pressure. The residue was refluxed with 1N HCl (20 ml) for 4 hours, the reaction cooled and washed with methylene chloride (2×20 ml). It was then brought to pH 14 by addition of 6N sodium hydroxide and extracted with the methylene chloride (3×20 ml). The combined extracts were dried (Na2SO4) and concentrated to give 0.600 g (60%) of title product, verified by its 1H-NMR spectrum. The reaction was then cooled The aqueous solution was extracted with methylene chloride (3×20 ml) concentrated under reduced pressure The residue was refluxed with 1N HCl (20 ml) for 4 hours the reaction cooled washed with methylene chloride (2×20 ml) It was then brought to pH 14 by addition of 6N sodium hydroxide extracted with the methylene chloride (3×20 ml) The combined extracts were dried (Na2SO4) concentrated

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: The 2,2,4,4-tetramethylthietan-3-one of Example 9, Step 1a, was converted to the corresponding oxime using hydroxylamine hydrochloride and sodium acetate by the procedure described in Example 12B of U.S. Pat. No. 4,411,925. The oxime (12.0 g., 0.045 moles) in 50 ml. of THF was added dropwise to a stirred suspension of LiAlH4 (6 g., 0.15 moles) in 50 ml. of THF at 0° C. After addition of the oxime was completed, the reaction mixture was allowed to warm to room temperature and was then refluxed for 1.5 hours. The reaction was carefully quenched by dropwise addition of 6 ml. of H2O, 6 ml. of 15% NaOH and 18 ml. of H2O. The quenched solution was filtered and the filtrate evaporated to give 8 g. of crude amine. The crude amine was purified by silica gel chromatography with 5% methanol/chloroform as the eluting solvent. Yield: 3.8 l g. at 0° C was then refluxed for 1.5 hours The reaction was carefully quenched by dropwise addition of 6 ml The quenched solution was filtered the filtrate evaporated to give 8 g The crude amine was purified by silica gel chromatography with 5% methanol/chloroform as the eluting solvent

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

实验步骤: The 2,2,4,4-tetramethylthietan-3-one of Example 9, Step 1a, was converted to the corresponding oxime using hydroxylamine hydrochloride and sodium acetate by the procedure described in Example 12B of U.S. Pat. No. 4,411,925. The oxime (12.0 g., 0.045 moles) in 50 ml. of THF was added dropwise to a stirred suspension of LiAlH4 (6 g., 0.15 moles) in 50 ml. of THF at 0° C. After addition of the oxime was completed, the reaction mixture was allowed to warm to room temperature and was then refluxed for 1.5 hours. The reaction was carefully quenched by dropwise addition of 6 ml. of H2O, 6 ml. of 15% NaOH and 18 ml. of H2O. The quenched solution was filtered and the filtrate evaporated to give 8 g. of crude amine. The crude amine was purified by silica gel chromatography with 5% methanol/chloroform as the eluting solvent. Yield: 3.8 l g. at 0° C was then refluxed for 1.5 hours The reaction was carefully quenched by dropwise addition of 6 ml The quenched solution was filtered the filtrate evaporated to give 8 g The crude amine was purified by silica gel chromatography with 5% methanol/chloroform as the eluting solvent

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

实验步骤: A solution of 14.53 g. (0.1 mole) 3-amino-2,2,4,4-tetramethylthietane and 64.17 g. (0.3 mole) sodium m-periodate in 500 ml. water was stirred overnight at room temperature. The reaction mixture was adjusted to pH 13 with sodium hydroxide solution and the precipitated sodium iodate removed by filtration. The filtrate was washed with 100 ml. ethyl ether, the aqueous phase extracted continuously with methylene chloride over 18 hours, the extract dried (MgSO4) and solvent evaporated in vacuo. The residual solid was recrystallized from ethyl acetate to provide 8.5 g. of product, M.P. 104°-106.5° C. A second crop of crystals was obtained, 2.7 g., M.P. 103°-106° C. Total yield, 63%. the precipitated sodium iodate removed by filtration The filtrate was washed with 100 ml ethyl ether, the aqueous phase extracted continuously with methylene chloride over 18 hours the extract dried (MgSO4) and solvent evaporated in vacuo The residual solid was recrystallized from ethyl acetate to provide 8.5 g A second crop of crystals was obtained

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

实验步骤: A solution of 14.53 g. (0.1 mole) 3-amino-2,2,4,4-tetramethylthietane and 64.17 g. (0.3 mole) sodium m-periodate in 500 ml. water was stirred overnight at room temperature. The reaction mixture was adjusted to pH 13 with sodium hydroxide solution and the precipitated sodium iodate removed by filtration. The filtrate was washed with 100 ml. ethyl ether, the aqueous phase extracted continuously with methylene chloride over 18 hours, the extract dried (MgSO4) and solvent evaporated in vacuo. The residual solid was recrystallized from ethyl acetate to provide 8.5 g. of product, M.P. 104°-106.5° C. A second crop of crystals was obtained, 2.7 g., M.P. 103°-106° C. Total yield, 63%. the precipitated sodium iodate removed by filtration The filtrate was washed with 100 ml ethyl ether, the aqueous phase extracted continuously with methylene chloride over 18 hours the extract dried (MgSO4) and solvent evaporated in vacuo The residual solid was recrystallized from ethyl acetate to provide 8.5 g A second crop of crystals was obtained