Structure of 73101-64-1
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CAS No. : | 73101-64-1 |
Formula : | C8H6NNaO4S |
M.W : | 235.19 |
SMILES Code : | O=S(CC1=NOC2=CC=CC=C12)([O-])=O.[Na+] |
MDL No. : | MFCD07782146 |
InChI Key : | QILCHBOPDIODSB-UHFFFAOYSA-M |
Pubchem ID : | 23674934 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P280-P305+P351+P338 |
Num. heavy atoms | 15 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.12 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 5.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 47.66 |
TPSA ? Topological Polar Surface Area: Calculated from |
91.61 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
-11.38 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.43 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.8 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.36 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.52 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
-1.65 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.88 |
Solubility | 3.09 mg/ml ; 0.0131 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.92 |
Solubility | 2.82 mg/ml ; 0.012 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.68 |
Solubility | 0.496 mg/ml ; 0.00211 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
No |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
Yes |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-7.43 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.85 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1) A mixture of hydroxylamine sulfate (43 g), water (113 ml) and a 25% aqueous sodium hydroxide solution (57 ml) is stirred, and thereto are added 4-hydroxycoumarin (21 g) and ethylenediamine-tetraacetic acid disodium salt dihydrate (0.4 g), and the mixture is stirred with heating at 84 C. to 86 C. for 4 hours. The reaction mixture is cooled, and thereto are added 1,2-dichloroethane (30 ml) and water (43 ml), and the mixture is stirred. The 1,2-dichloroethane layer is removed, and the pH value thereof is adjusted to pH 1-2 with 62.5% sulfuric acid. The mixture is extracted twice with 1,2-dichloroethane (120 ml and 10 ml) to give a mixture of <strong>[4865-84-3]1,2-benzisoxazole-3-acetic acid</strong> and 1,2-dichloroethane. The purity of <strong>[4865-84-3]1,2-benzisoxazole-3-acetic acid</strong> in this mixture is 98%. 2) Water is removed by distillation from the above mixture of <strong>[4865-84-3]1,2-benzisoxazole-3-acetic acid</strong> and 1,2-dichloroethane, and thereto is added dropwise chlorosulfonic acid (15.5 g) while the internal temperature is kept at 63 C.-79 C. After the addition, the mixture is stirred for 90 minutes while the reaction temperature is kept at 63 C.-79 C. After cooling, a 25% aqueous sodium hydroxide solution is added to the reaction mixture so as to adjust the pH value thereof to pH 11 or above. Water is removed by distillation from the reaction mixture to give a mixture of sodium 1,2-benzisoxazole-3-methanesulfonate and 1,2-dichloroethane. Triethylamine (2.4 g) and phosphoryl chloride (17.5 g) are added to this mixture, and the mixture is stirred at a temperature of 77 C.-83 C. for 6 hours. After cooling, to the reaction mixture is added 1,2-dichloroethane (80 ml), and ammonia gas is blown into the mixture until saturated while the reaction temperature is kept at 30 C.-60 C. The reaction mixture is concentrated, and water is added thereto. The mixture is stirred, and the precipitated crystals are collected by filtration, and washed with water to give crude crystals of 1,2-benzisoxazole-3-methanesulfonamide. The purity of the crude crystals is 96%. 3) The above crude crystals are recrystallized from a 50% aqueous isopropanol, and dried at 80 C. for 16 hours to give crystals of 1,2-benzisoxazole-3-methanesulfonamide having a purity of 99%. | ||
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%). | ||
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%). |
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. | ||
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. | ||
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. | ||
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. | ||
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. | ||
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. | ||
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. | ||
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. | ||
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. | ||
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. | ||
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. | ||
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. | ||
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. | ||
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. | ||
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. |