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Example 10 To a mixture of <strong>[4865-84-3]1,2-benzisoxazole-3-acetic acid</strong> (1.77 g), ethyl acetate (2.64 g) and toluene (15 ml) was added dropwise a solution of chlorosulfonic acid (1.75 g) in dichloromethane (5 ml) with stirring at room temperature and the resulting mixture was heated with stirring at 70 C. for 2 hours. It was confirmed that 84%, 5% and 7% of 1,2-benzisoxazole-3-methane sulfonic acid, starting material and a by-product respectively, were present in the reaction solution. Water was added to the reaction mixture and the mixture was extracted with aqueous layer. The aqueous layer was adjusted with 25% aqueous sodium hydroxide to pH. 10 and concentrated under reduced pressure. To the residue was added water until the total weight became approximately 7 g and the mixture was cooled in an ice water bath. The precipitated crystals were collected by filtration and dried at room temperature to give 2.38 9 of sodium 1,2-benzisoxazole-3-methane sulfonate (purity of 96%). Examples 11-13; 1,2-Benzisoxazole-3-acetic acid (1.77 grams) was treated in a similar manner in Example 10 to give the following results in Table 3. TABLE 3 Contents in a reaction mixture Chlorosulfonic Desired Starting By- Yield Example Toluene acid Solvent Lewis base compound materialproduct1) (Purity) 10 15 ml 1.75 g Dichloroethane Ethyl 84% 5% 7% 2.38 g 5 ml acetate (96%) 2.64 g 11 15 ml 1.75 g Chloroform Ethyl 86% 4% 6% 2.41 g 5 ml acetate (96%) 2.64 g 12 15 ml 1.75 g 1,2-Dichloroethane Acetonitrile 78% 5% 9% - 5 ml 1.23 g 13 15 ml 2.10 g 1,2-Dichloroethane tert-Butyl 74% 11% 12% - 5 ml cyanide 2.49 g 1)A reaction product of toluene with chlorosulfonic acid. |
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Example 1; To a mixture of <strong>[4865-84-3]1,2-benzisoxazole-3-acetic acid</strong> (1.77 g), ethyl isobutyrate (3.48 g) and toluene (15 ml) was added dropwise chlorosulfonic acid (1.40 g) with stirring at room temperature and the resulting mixture was heated with stirring at 80 C. for 2 hours. It was confirmed that there were 70%, 21% and 8% of 1,2-benzisoxazole-3-methane sulfonic acid, starting material and a by-product, respectively, in the reaction solution. Water was added to the reaction mixture and the mixture was extracted with aqueous layer. The aqueous layer was adjusted with 25% aqueous sodium hydroxide to pH 10 and concentrated under reduced pressure. To the residue was added water until total weight became approximately 7 g and the mixture was cooled in an ice water bath. The precipitated crystals were collected by filtration and dried at room temperature to give 1.23 g of sodium 1,2-benzisoxazole-3-methanesulfonate (purity of 99%). ; Examples 2-9; 1,2-Benzisoxazole-3-acetic acid (1.77 g) was treated in a similar manner in Example 1 to give the following results in Table 1. TABLE 1 Contents in a reaction mixture Chlorosulfonic Desired Starting By- Yield Example Toluene acid Lewis base compound materialproduct1) (Purity) 1 15 ml 1.40 g Ethyl isobutyrate 70% 21% 8% 1.23 g 3.48 g (99%) 2 15 ml 1.40 g Ethyl acetate 67% 26% 6% 1.48 g 2.64 g (90%) 3 15 ml 1.75 g Ethyl acetate 64% 23% 12% 1.75 g 2.64 g (94%) 4 15 ml 1.40 g Ethyl propionate 63% 28% 7% 1.29 g 3.06 g (93%) 5 15 ml 1.40 g Methyl pivalate 60% 25% 8% 1.21 g 3.48 g (93%) 6 15 ml 1.40 g Ethyl pivalate 62% 29% 9% - 3.91 g 7 15 ml 1.40 g Ethyl benzoate 63% 28% 9% 1.29 g 4.51 g (91%) 8 18 ml 1.40 g Benzonitrile 53% 23% 8% 1.25 g 1.55 g (91%) 9 18 ml 1.40 g tert-Butyl cyanide 66% 23% 8% 1.12 g 1.25 g (92%) 1)A reaction product with toluene and chlorosulfonic acid. |
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Example 1; To a mixture of <strong>[4865-84-3]1,2-benzisoxazole-3-acetic acid</strong> (1.77 g), ethyl isobutyrate (3.48 g) and toluene (15 ml) was added dropwise chlorosulfonic acid (1.40 g) with stirring at room temperature and the resulting mixture was heated with stirring at 80 C. for 2 hours. It was confirmed that there were 70%, 21% and 8% of 1,2-benzisoxazole-3-methane sulfonic acid, starting material and a by-product, respectively, in the reaction solution. Water was added to the reaction mixture and the mixture was extracted with aqueous layer. The aqueous layer was adjusted with 25% aqueous sodium hydroxide to pH 10 and concentrated under reduced pressure. To the residue was added water until total weight became approximately 7 g and the mixture was cooled in an ice water bath. The precipitated crystals were collected by filtration and dried at room temperature to give 1.23 g of sodium 1,2-benzisoxazole-3-methanesulfonate (purity of 99%). ; Reference Examples 1-5; 1,2-Benzisoxazole-3-acetic acid (1.77 grams) was treated in a similar manner in Example 1 to give the following results in Table 2. TABLE 2 Contents in a reaction mixture Reference Chlorosulfonic Desired Starting By- Yield Example Toluene acid Lewis base compound materialproduct1) (Purity) 1 18 ml 1.40 g 1,4-Dioxane 81% 12% 5% 1.59 g 1.32 g (92%) 2 15 ml 1.40 g 1,2-Diethoxyethane 51% 24%5%, 18%2) - 3.54 g 3 18 ml 1.40 g DMF 3% 88% 9% - 1.10 g 4 36 ml 2.10 g 1-methyl-2-pyrrolidone 4% 80% 13% - 2.23 g 5 18 ml 2.33 g none 25% 29% 44% - 1)A reaction product of toluene with chlorosulfonic acid. 2)By-products other than a reaction product of toluene with chlorosulfonic acid. |
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Example 1; To a mixture of <strong>[4865-84-3]1,2-benzisoxazole-3-acetic acid</strong> (1.77 g), ethyl isobutyrate (3.48 g) and toluene (15 ml) was added dropwise chlorosulfonic acid (1.40 g) with stirring at room temperature and the resulting mixture was heated with stirring at 80 C. for 2 hours. It was confirmed that there were 70%, 21% and 8% of 1,2-benzisoxazole-3-methane sulfonic acid, starting material and a by-product, respectively, in the reaction solution. Water was added to the reaction mixture and the mixture was extracted with aqueous layer. The aqueous layer was adjusted with 25% aqueous sodium hydroxide to pH 10 and concentrated under reduced pressure. To the residue was added water until total weight became approximately 7 g and the mixture was cooled in an ice water bath. The precipitated crystals were collected by filtration and dried at room temperature to give 1.23 g of sodium 1,2-benzisoxazole-3-methanesulfonate (purity of 99%). ; Reference Examples 1-5; 1,2-Benzisoxazole-3-acetic acid (1.77 grams) was treated in a similar manner in Example 1 to give the following results in Table 2. TABLE 2 Contents in a reaction mixture Reference Chlorosulfonic Desired Starting By- Yield Example Toluene acid Lewis base compound materialproduct1) (Purity) 1 18 ml 1.40 g 1,4-Dioxane 81% 12% 5% 1.59 g 1.32 g (92%) 2 15 ml 1.40 g 1,2-Diethoxyethane 51% 24%5%, 18%2) - 3.54 g 3 18 ml 1.40 g DMF 3% 88% 9% - 1.10 g 4 36 ml 2.10 g 1-methyl-2-pyrrolidone 4% 80% 13% - 2.23 g 5 18 ml 2.33 g none 25% 29% 44% - 1)A reaction product of toluene with chlorosulfonic acid. 2)By-products other than a reaction product of toluene with chlorosulfonic acid. |
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Example 1; To a mixture of <strong>[4865-84-3]1,2-benzisoxazole-3-acetic acid</strong> (1.77 g), ethyl isobutyrate (3.48 g) and toluene (15 ml) was added dropwise chlorosulfonic acid (1.40 g) with stirring at room temperature and the resulting mixture was heated with stirring at 80 C. for 2 hours. It was confirmed that there were 70%, 21% and 8% of 1,2-benzisoxazole-3-methane sulfonic acid, starting material and a by-product, respectively, in the reaction solution. Water was added to the reaction mixture and the mixture was extracted with aqueous layer. The aqueous layer was adjusted with 25% aqueous sodium hydroxide to pH 10 and concentrated under reduced pressure. To the residue was added water until total weight became approximately 7 g and the mixture was cooled in an ice water bath. The precipitated crystals were collected by filtration and dried at room temperature to give 1.23 g of sodium 1,2-benzisoxazole-3-methanesulfonate (purity of 99%). ; Reference Examples 1-5; 1,2-Benzisoxazole-3-acetic acid (1.77 grams) was treated in a similar manner in Example 1 to give the following results in Table 2. TABLE 2 Contents in a reaction mixture Reference Chlorosulfonic Desired Starting By- Yield Example Toluene acid Lewis base compound materialproduct1) (Purity) 1 18 ml 1.40 g 1,4-Dioxane 81% 12% 5% 1.59 g 1.32 g (92%) 2 15 ml 1.40 g 1,2-Diethoxyethane 51% 24%5%, 18%2) - 3.54 g 3 18 ml 1.40 g DMF 3% 88% 9% - 1.10 g 4 36 ml 2.10 g 1-methyl-2-pyrrolidone 4% 80% 13% - 2.23 g 5 18 ml 2.33 g none 25% 29% 44% - 1)A reaction product of toluene with chlorosulfonic acid. 2)By-products other than a reaction product of toluene with chlorosulfonic acid. |
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Example 10 To a mixture of <strong>[4865-84-3]1,2-benzisoxazole-3-acetic acid</strong> (1.77 g), ethyl acetate (2.64 g) and toluene (15 ml) was added dropwise a solution of chlorosulfonic acid (1.75 g) in dichloromethane (5 ml) with stirring at room temperature and the resulting mixture was heated with stirring at 70 C. for 2 hours. It was confirmed that 84%, 5% and 7% of 1,2-benzisoxazole-3-methane sulfonic acid, starting material and a by-product respectively, were present in the reaction solution. Water was added to the reaction mixture and the mixture was extracted with aqueous layer. The aqueous layer was adjusted with 25% aqueous sodium hydroxide to pH. 10 and concentrated under reduced pressure. To the residue was added water until the total weight became approximately 7 g and the mixture was cooled in an ice water bath. The precipitated crystals were collected by filtration and dried at room temperature to give 2.38 9 of sodium 1,2-benzisoxazole-3-methane sulfonate (purity of 96%). Examples 11-13; 1,2-Benzisoxazole-3-acetic acid (1.77 grams) was treated in a similar manner in Example 10 to give the following results in Table 3. TABLE 3 Contents in a reaction mixture Chlorosulfonic Desired Starting By- Yield Example Toluene acid Solvent Lewis base compound materialproduct1) (Purity) 10 15 ml 1.75 g Dichloroethane Ethyl 84% 5% 7% 2.38 g 5 ml acetate (96%) 2.64 g 11 15 ml 1.75 g Chloroform Ethyl 86% 4% 6% 2.41 g 5 ml acetate (96%) 2.64 g 12 15 ml 1.75 g 1,2-Dichloroethane Acetonitrile 78% 5% 9% - 5 ml 1.23 g 13 15 ml 2.10 g 1,2-Dichloroethane tert-Butyl 74% 11% 12% - 5 ml cyanide 2.49 g 1)A reaction product of toluene with chlorosulfonic acid. |
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Example 10 To a mixture of <strong>[4865-84-3]1,2-benzisoxazole-3-acetic acid</strong> (1.77 g), ethyl acetate (2.64 g) and toluene (15 ml) was added dropwise a solution of chlorosulfonic acid (1.75 g) in dichloromethane (5 ml) with stirring at room temperature and the resulting mixture was heated with stirring at 70 C. for 2 hours. It was confirmed that 84%, 5% and 7% of 1,2-benzisoxazole-3-methane sulfonic acid, starting material and a by-product respectively, were present in the reaction solution. Water was added to the reaction mixture and the mixture was extracted with aqueous layer. The aqueous layer was adjusted with 25% aqueous sodium hydroxide to pH. 10 and concentrated under reduced pressure. To the residue was added water until the total weight became approximately 7 g and the mixture was cooled in an ice water bath. The precipitated crystals were collected by filtration and dried at room temperature to give 2.38 9 of sodium 1,2-benzisoxazole-3-methane sulfonate (purity of 96%). Examples 11-13; 1,2-Benzisoxazole-3-acetic acid (1.77 grams) was treated in a similar manner in Example 10 to give the following results in Table 3. TABLE 3 Contents in a reaction mixture Chlorosulfonic Desired Starting By- Yield Example Toluene acid Solvent Lewis base compound materialproduct1) (Purity) 10 15 ml 1.75 g Dichloroethane Ethyl 84% 5% 7% 2.38 g 5 ml acetate (96%) 2.64 g 11 15 ml 1.75 g Chloroform Ethyl 86% 4% 6% 2.41 g 5 ml acetate (96%) 2.64 g 12 15 ml 1.75 g 1,2-Dichloroethane Acetonitrile 78% 5% 9% - 5 ml 1.23 g 13 15 ml 2.10 g 1,2-Dichloroethane tert-Butyl 74% 11% 12% - 5 ml cyanide 2.49 g 1)A reaction product of toluene with chlorosulfonic acid. |
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Example 1; To a mixture of <strong>[4865-84-3]1,2-benzisoxazole-3-acetic acid</strong> (1.77 g), ethyl isobutyrate (3.48 g) and toluene (15 ml) was added dropwise chlorosulfonic acid (1.40 g) with stirring at room temperature and the resulting mixture was heated with stirring at 80 C. for 2 hours. It was confirmed that there were 70%, 21% and 8% of 1,2-benzisoxazole-3-methane sulfonic acid, starting material and a by-product, respectively, in the reaction solution. Water was added to the reaction mixture and the mixture was extracted with aqueous layer. The aqueous layer was adjusted with 25% aqueous sodium hydroxide to pH 10 and concentrated under reduced pressure. To the residue was added water until total weight became approximately 7 g and the mixture was cooled in an ice water bath. The precipitated crystals were collected by filtration and dried at room temperature to give 1.23 g of sodium 1,2-benzisoxazole-3-methanesulfonate (purity of 99%). ; Examples 2-9; 1,2-Benzisoxazole-3-acetic acid (1.77 g) was treated in a similar manner in Example 1 to give the following results in Table 1. TABLE 1 Contents in a reaction mixture Chlorosulfonic Desired Starting By- Yield Example Toluene acid Lewis base compound materialproduct1) (Purity) 1 15 ml 1.40 g Ethyl isobutyrate 70% 21% 8% 1.23 g 3.48 g (99%) 2 15 ml 1.40 g Ethyl acetate 67% 26% 6% 1.48 g 2.64 g (90%) 3 15 ml 1.75 g Ethyl acetate 64% 23% 12% 1.75 g 2.64 g (94%) 4 15 ml 1.40 g Ethyl propionate 63% 28% 7% 1.29 g 3.06 g (93%) 5 15 ml 1.40 g Methyl pivalate 60% 25% 8% 1.21 g 3.48 g (93%) 6 15 ml 1.40 g Ethyl pivalate 62% 29% 9% - 3.91 g 7 15 ml 1.40 g Ethyl benzoate 63% 28% 9% 1.29 g 4.51 g (91%) 8 18 ml 1.40 g Benzonitrile 53% 23% 8% 1.25 g 1.55 g (91%) 9 18 ml 1.40 g tert-Butyl cyanide 66% 23% 8% 1.12 g 1.25 g (92%) 1)A reaction product with toluene and chlorosulfonic acid. |
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Example 1; To a mixture of <strong>[4865-84-3]1,2-benzisoxazole-3-acetic acid</strong> (1.77 g), ethyl isobutyrate (3.48 g) and toluene (15 ml) was added dropwise chlorosulfonic acid (1.40 g) with stirring at room temperature and the resulting mixture was heated with stirring at 80 C. for 2 hours. It was confirmed that there were 70%, 21% and 8% of 1,2-benzisoxazole-3-methane sulfonic acid, starting material and a by-product, respectively, in the reaction solution. Water was added to the reaction mixture and the mixture was extracted with aqueous layer. The aqueous layer was adjusted with 25% aqueous sodium hydroxide to pH 10 and concentrated under reduced pressure. To the residue was added water until total weight became approximately 7 g and the mixture was cooled in an ice water bath. The precipitated crystals were collected by filtration and dried at room temperature to give 1.23 g of sodium 1,2-benzisoxazole-3-methanesulfonate (purity of 99%). ; Examples 2-9; 1,2-Benzisoxazole-3-acetic acid (1.77 g) was treated in a similar manner in Example 1 to give the following results in Table 1. TABLE 1 Contents in a reaction mixture Chlorosulfonic Desired Starting By- Yield Example Toluene acid Lewis base compound materialproduct1) (Purity) 1 15 ml 1.40 g Ethyl isobutyrate 70% 21% 8% 1.23 g 3.48 g (99%) 2 15 ml 1.40 g Ethyl acetate 67% 26% 6% 1.48 g 2.64 g (90%) 3 15 ml 1.75 g Ethyl acetate 64% 23% 12% 1.75 g 2.64 g (94%) 4 15 ml 1.40 g Ethyl propionate 63% 28% 7% 1.29 g 3.06 g (93%) 5 15 ml 1.40 g Methyl pivalate 60% 25% 8% 1.21 g 3.48 g (93%) 6 15 ml 1.40 g Ethyl pivalate 62% 29% 9% - 3.91 g 7 15 ml 1.40 g Ethyl benzoate 63% 28% 9% 1.29 g 4.51 g (91%) 8 18 ml 1.40 g Benzonitrile 53% 23% 8% 1.25 g 1.55 g (91%) 9 18 ml 1.40 g tert-Butyl cyanide 66% 23% 8% 1.12 g 1.25 g (92%) 1)A reaction product with toluene and chlorosulfonic acid. |
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Example 1; To a mixture of <strong>[4865-84-3]1,2-benzisoxazole-3-acetic acid</strong> (1.77 g), ethyl isobutyrate (3.48 g) and toluene (15 ml) was added dropwise chlorosulfonic acid (1.40 g) with stirring at room temperature and the resulting mixture was heated with stirring at 80 C. for 2 hours. It was confirmed that there were 70%, 21% and 8% of 1,2-benzisoxazole-3-methane sulfonic acid, starting material and a by-product, respectively, in the reaction solution. Water was added to the reaction mixture and the mixture was extracted with aqueous layer. The aqueous layer was adjusted with 25% aqueous sodium hydroxide to pH 10 and concentrated under reduced pressure. To the residue was added water until total weight became approximately 7 g and the mixture was cooled in an ice water bath. The precipitated crystals were collected by filtration and dried at room temperature to give 1.23 g of sodium 1,2-benzisoxazole-3-methanesulfonate (purity of 99%). ; Examples 2-9; 1,2-Benzisoxazole-3-acetic acid (1.77 g) was treated in a similar manner in Example 1 to give the following results in Table 1. TABLE 1 Contents in a reaction mixture Chlorosulfonic Desired Starting By- Yield Example Toluene acid Lewis base compound materialproduct1) (Purity) 1 15 ml 1.40 g Ethyl isobutyrate 70% 21% 8% 1.23 g 3.48 g (99%) 2 15 ml 1.40 g Ethyl acetate 67% 26% 6% 1.48 g 2.64 g (90%) 3 15 ml 1.75 g Ethyl acetate 64% 23% 12% 1.75 g 2.64 g (94%) 4 15 ml 1.40 g Ethyl propionate 63% 28% 7% 1.29 g 3.06 g (93%) 5 15 ml 1.40 g Methyl pivalate 60% 25% 8% 1.21 g 3.48 g (93%) 6 15 ml 1.40 g Ethyl pivalate 62% 29% 9% - 3.91 g 7 15 ml 1.40 g Ethyl benzoate 63% 28% 9% 1.29 g 4.51 g (91%) 8 18 ml 1.40 g Benzonitrile 53% 23% 8% 1.25 g 1.55 g (91%) 9 18 ml 1.40 g tert-Butyl cyanide 66% 23% 8% 1.12 g 1.25 g (92%) 1)A reaction product with toluene and chlorosulfonic acid. |
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Example 1; To a mixture of <strong>[4865-84-3]1,2-benzisoxazole-3-acetic acid</strong> (1.77 g), ethyl isobutyrate (3.48 g) and toluene (15 ml) was added dropwise chlorosulfonic acid (1.40 g) with stirring at room temperature and the resulting mixture was heated with stirring at 80 C. for 2 hours. It was confirmed that there were 70%, 21% and 8% of 1,2-benzisoxazole-3-methane sulfonic acid, starting material and a by-product, respectively, in the reaction solution. Water was added to the reaction mixture and the mixture was extracted with aqueous layer. The aqueous layer was adjusted with 25% aqueous sodium hydroxide to pH 10 and concentrated under reduced pressure. To the residue was added water until total weight became approximately 7 g and the mixture was cooled in an ice water bath. The precipitated crystals were collected by filtration and dried at room temperature to give 1.23 g of sodium 1,2-benzisoxazole-3-methanesulfonate (purity of 99%). ; Examples 2-9; 1,2-Benzisoxazole-3-acetic acid (1.77 g) was treated in a similar manner in Example 1 to give the following results in Table 1. TABLE 1 Contents in a reaction mixture Chlorosulfonic Desired Starting By- Yield Example Toluene acid Lewis base compound materialproduct1) (Purity) 1 15 ml 1.40 g Ethyl isobutyrate 70% 21% 8% 1.23 g 3.48 g (99%) 2 15 ml 1.40 g Ethyl acetate 67% 26% 6% 1.48 g 2.64 g (90%) 3 15 ml 1.75 g Ethyl acetate 64% 23% 12% 1.75 g 2.64 g (94%) 4 15 ml 1.40 g Ethyl propionate 63% 28% 7% 1.29 g 3.06 g (93%) 5 15 ml 1.40 g Methyl pivalate 60% 25% 8% 1.21 g 3.48 g (93%) 6 15 ml 1.40 g Ethyl pivalate 62% 29% 9% - 3.91 g 7 15 ml 1.40 g Ethyl benzoate 63% 28% 9% 1.29 g 4.51 g (91%) 8 18 ml 1.40 g Benzonitrile 53% 23% 8% 1.25 g 1.55 g (91%) 9 18 ml 1.40 g tert-Butyl cyanide 66% 23% 8% 1.12 g 1.25 g (92%) 1)A reaction product with toluene and chlorosulfonic acid. |
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Example 1; To a mixture of <strong>[4865-84-3]1,2-benzisoxazole-3-acetic acid</strong> (1.77 g), ethyl isobutyrate (3.48 g) and toluene (15 ml) was added dropwise chlorosulfonic acid (1.40 g) with stirring at room temperature and the resulting mixture was heated with stirring at 80 C. for 2 hours. It was confirmed that there were 70%, 21% and 8% of 1,2-benzisoxazole-3-methane sulfonic acid, starting material and a by-product, respectively, in the reaction solution. Water was added to the reaction mixture and the mixture was extracted with aqueous layer. The aqueous layer was adjusted with 25% aqueous sodium hydroxide to pH 10 and concentrated under reduced pressure. To the residue was added water until total weight became approximately 7 g and the mixture was cooled in an ice water bath. The precipitated crystals were collected by filtration and dried at room temperature to give 1.23 g of sodium 1,2-benzisoxazole-3-methanesulfonate (purity of 99%). ; Examples 2-9; 1,2-Benzisoxazole-3-acetic acid (1.77 g) was treated in a similar manner in Example 1 to give the following results in Table 1. TABLE 1 Contents in a reaction mixture Chlorosulfonic Desired Starting By- Yield Example Toluene acid Lewis base compound materialproduct1) (Purity) 1 15 ml 1.40 g Ethyl isobutyrate 70% 21% 8% 1.23 g 3.48 g (99%) 2 15 ml 1.40 g Ethyl acetate 67% 26% 6% 1.48 g 2.64 g (90%) 3 15 ml 1.75 g Ethyl acetate 64% 23% 12% 1.75 g 2.64 g (94%) 4 15 ml 1.40 g Ethyl propionate 63% 28% 7% 1.29 g 3.06 g (93%) 5 15 ml 1.40 g Methyl pivalate 60% 25% 8% 1.21 g 3.48 g (93%) 6 15 ml 1.40 g Ethyl pivalate 62% 29% 9% - 3.91 g 7 15 ml 1.40 g Ethyl benzoate 63% 28% 9% 1.29 g 4.51 g (91%) 8 18 ml 1.40 g Benzonitrile 53% 23% 8% 1.25 g 1.55 g (91%) 9 18 ml 1.40 g tert-Butyl cyanide 66% 23% 8% 1.12 g 1.25 g (92%) 1)A reaction product with toluene and chlorosulfonic acid. |
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Example 1; To a mixture of <strong>[4865-84-3]1,2-benzisoxazole-3-acetic acid</strong> (1.77 g), ethyl isobutyrate (3.48 g) and toluene (15 ml) was added dropwise chlorosulfonic acid (1.40 g) with stirring at room temperature and the resulting mixture was heated with stirring at 80 C. for 2 hours. It was confirmed that there were 70%, 21% and 8% of 1,2-benzisoxazole-3-methane sulfonic acid, starting material and a by-product, respectively, in the reaction solution. Water was added to the reaction mixture and the mixture was extracted with aqueous layer. The aqueous layer was adjusted with 25% aqueous sodium hydroxide to pH 10 and concentrated under reduced pressure. To the residue was added water until total weight became approximately 7 g and the mixture was cooled in an ice water bath. The precipitated crystals were collected by filtration and dried at room temperature to give 1.23 g of sodium 1,2-benzisoxazole-3-methanesulfonate (purity of 99%). ; Reference Examples 1-5; 1,2-Benzisoxazole-3-acetic acid (1.77 grams) was treated in a similar manner in Example 1 to give the following results in Table 2. TABLE 2 Contents in a reaction mixture Reference Chlorosulfonic Desired Starting By- Yield Example Toluene acid Lewis base compound materialproduct1) (Purity) 1 18 ml 1.40 g 1,4-Dioxane 81% 12% 5% 1.59 g 1.32 g (92%) 2 15 ml 1.40 g 1,2-Diethoxyethane 51% 24%5%, 18%2) - 3.54 g 3 18 ml 1.40 g DMF 3% 88% 9% - 1.10 g 4 36 ml 2.10 g 1-methyl-2-pyrrolidone 4% 80% 13% - 2.23 g 5 18 ml 2.33 g none 25% 29% 44% - 1)A reaction product of toluene with chlorosulfonic acid. 2)By-products other than a reaction product of toluene with chlorosulfonic acid. |
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Example 1; To a mixture of <strong>[4865-84-3]1,2-benzisoxazole-3-acetic acid</strong> (1.77 g), ethyl isobutyrate (3.48 g) and toluene (15 ml) was added dropwise chlorosulfonic acid (1.40 g) with stirring at room temperature and the resulting mixture was heated with stirring at 80 C. for 2 hours. It was confirmed that there were 70%, 21% and 8% of 1,2-benzisoxazole-3-methane sulfonic acid, starting material and a by-product, respectively, in the reaction solution. Water was added to the reaction mixture and the mixture was extracted with aqueous layer. The aqueous layer was adjusted with 25% aqueous sodium hydroxide to pH 10 and concentrated under reduced pressure. To the residue was added water until total weight became approximately 7 g and the mixture was cooled in an ice water bath. The precipitated crystals were collected by filtration and dried at room temperature to give 1.23 g of sodium 1,2-benzisoxazole-3-methanesulfonate (purity of 99%). ; Examples 2-9; 1,2-Benzisoxazole-3-acetic acid (1.77 g) was treated in a similar manner in Example 1 to give the following results in Table 1. TABLE 1 Contents in a reaction mixture Chlorosulfonic Desired Starting By- Yield Example Toluene acid Lewis base compound materialproduct1) (Purity) 1 15 ml 1.40 g Ethyl isobutyrate 70% 21% 8% 1.23 g 3.48 g (99%) 2 15 ml 1.40 g Ethyl acetate 67% 26% 6% 1.48 g 2.64 g (90%) 3 15 ml 1.75 g Ethyl acetate 64% 23% 12% 1.75 g 2.64 g (94%) 4 15 ml 1.40 g Ethyl propionate 63% 28% 7% 1.29 g 3.06 g (93%) 5 15 ml 1.40 g Methyl pivalate 60% 25% 8% 1.21 g 3.48 g (93%) 6 15 ml 1.40 g Ethyl pivalate 62% 29% 9% - 3.91 g 7 15 ml 1.40 g Ethyl benzoate 63% 28% 9% 1.29 g 4.51 g (91%) 8 18 ml 1.40 g Benzonitrile 53% 23% 8% 1.25 g 1.55 g (91%) 9 18 ml 1.40 g tert-Butyl cyanide 66% 23% 8% 1.12 g 1.25 g (92%) 1)A reaction product with toluene and chlorosulfonic acid. |
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Example 1; To a mixture of <strong>[4865-84-3]1,2-benzisoxazole-3-acetic acid</strong> (1.77 g), ethyl isobutyrate (3.48 g) and toluene (15 ml) was added dropwise chlorosulfonic acid (1.40 g) with stirring at room temperature and the resulting mixture was heated with stirring at 80 C. for 2 hours. It was confirmed that there were 70%, 21% and 8% of 1,2-benzisoxazole-3-methane sulfonic acid, starting material and a by-product, respectively, in the reaction solution. Water was added to the reaction mixture and the mixture was extracted with aqueous layer. The aqueous layer was adjusted with 25% aqueous sodium hydroxide to pH 10 and concentrated under reduced pressure. To the residue was added water until total weight became approximately 7 g and the mixture was cooled in an ice water bath. The precipitated crystals were collected by filtration and dried at room temperature to give 1.23 g of sodium 1,2-benzisoxazole-3-methanesulfonate (purity of 99%). ; Reference Examples 1-5; 1,2-Benzisoxazole-3-acetic acid (1.77 grams) was treated in a similar manner in Example 1 to give the following results in Table 2. TABLE 2 Contents in a reaction mixture Reference Chlorosulfonic Desired Starting By- Yield Example Toluene acid Lewis base compound materialproduct1) (Purity) 1 18 ml 1.40 g 1,4-Dioxane 81% 12% 5% 1.59 g 1.32 g (92%) 2 15 ml 1.40 g 1,2-Diethoxyethane 51% 24%5%, 18%2) - 3.54 g 3 18 ml 1.40 g DMF 3% 88% 9% - 1.10 g 4 36 ml 2.10 g 1-methyl-2-pyrrolidone 4% 80% 13% - 2.23 g 5 18 ml 2.33 g none 25% 29% 44% - 1)A reaction product of toluene with chlorosulfonic acid. 2)By-products other than a reaction product of toluene with chlorosulfonic acid. |