* 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.
With hydroxylamine hydrochloride; triethylamine In water; dimethyl sulfoxide at 50℃; for 3 h;
General procedure: Methyl 5-nitrosalicylate (0.79 g, 4 mmol) in DMSO (8 ml) and hydroxylamine hydrochloride (0.60 g, 8,6 mmol) in H2O (2 ml) were mixed followed by addition of triethylamine (0.80 g, 8 mmol) and mixture was incubated for 3 h at 50 °C. The solution was cooled and poured into water (30 ml) and unreacted ester was removed by filtration. Filtrate was extracted by ethylacetate (50 ml), organic phase was washed with water (40 ml) and brine (40 ml) and dried over Na2SO4. The solvent was removed at reduced pressure, and the raw product that was finally purified by washing with MeCN (3 ml). Yield 30 percent.
Reference:
[1] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 21, p. 5936 - 5940
[2] Journal of Medicinal Chemistry, 2008, vol. 51, # 12, p. 3357 - 3359
[3] Tetrahedron Letters, 2016, vol. 57, # 48, p. 5301 - 5303
With hydroxylamine hydrochloride; triethylamine; In water; dimethyl sulfoxide; at 50℃; for 3.0h;
General procedure: Methyl 5-nitrosalicylate (0.79 g, 4 mmol) in DMSO (8 ml) and hydroxylamine hydrochloride (0.60 g, 8,6 mmol) in H2O (2 ml) were mixed followed by addition of triethylamine (0.80 g, 8 mmol) and mixture was incubated for 3 h at 50 C. The solution was cooled and poured into water (30 ml) and unreacted ester was removed by filtration. Filtrate was extracted by ethylacetate (50 ml), organic phase was washed with water (40 ml) and brine (40 ml) and dried over Na2SO4. The solvent was removed at reduced pressure, and the raw product that was finally purified by washing with MeCN (3 ml). Yield 30 %.
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 20℃; for 0.533333h;Inert atmosphere;
General procedure: Salicylhydroxamic acid 1a (77 mg, 0.5 mmol, 1 equiv) was dissolved in anhydrous THF (7 mL) under an inert (N2) atmosphere. Triphenylphosphine (164 mg, 0.625 mmol, 1.25 equiv) was then added. After 2 min, DIAD (123 lL, 0.625 mmol, 1.25 equiv) was added dropwise. TLC (Hex/EtOAc, 1:3) after 30 min revealed the reaction was complete. The THF was removed in vacuo. The residue was partitioned between 0.1 M NaOH (50 mL)and CH2Cl2 (100 mL). The organic layer was separated, then the aqueous layerwas washed a further three times with CH2Cl2 (100 mL). The aqueous layer was acidified with 1 M HCl (10 mL), then extracted into CH2Cl2 (2 100 mL),washed with brine (50 mL), dried (Na2SO4), filtered and concentrated to yield the 3-hydroxybenzisoxazole 2a.
Catalytic DMF (4 drops) was added at rt to a solution of 5-nitrosalicylic acid (commercial, 5.00 g, 27.3 mmol) in thionyl chloride (50 mL). The reaction mixture was heated at reflux for 4h, then concentrated under vacuum. The residue was taken up in dioxane (20 mL) and a solution of 50% hydroxylamine in water (10 mL, 164 mmol) was added at 0 C. The reaction mixture was then stirred at rt and diluted with Et.20. The obtained precipitate was filtered off and rinsed with Et^O to afford 7.13 g of 2-hydroxy-5-nitro- benzenecarbohydroxamic acid a12, which was used in next step without any further purification. Yield (crude): quantitative.
With 1,1'-carbonyldiimidazole; In tetrahydrofuran;Reflux;
A solution of <strong>[61494-42-6]2-hydroxy-5-nitro-benzenecarbohydroxamic acid</strong> a12 (3.00 g, 15.1 mmol) in THF (60 mL) was heated at reflux, then a solution of 1 , 1 '-carbodiimidazole (4.91 g, 30.3 mmol) in THF (40 mL) was added at reflux. The reaction mixture was heated at reflux overnight, then concentrated under vacuum. The residue was taken up with water, then the mixture was acidified to pH1 with concentrated HCI and filtered. The filtrate was diluted with EtOAc and water. The organic layer was extracted with an aqueous saturated solution of NaHC03. The aqueous layer was then acidified to pH2 with concentrated HCI. The resulting precipitate was filtered off to afford 788 mg of 5-nitro-1 ,2-benzoxazol-3-one a13. Yield: 29%. 1H NMR (400 MHz, DMSO-cfe) delta 13.04 (s, 1 H), 8.73 (d, J = 2.4 Hz, 1 H), 8.46 (dd, J = 9.2, 2.4 Hz, 1 H), 7.81 (d, J = 9.2 Hz, 1 H).