* 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.
To the solution of 4a (Ig, 14.5mmol) in trifluoroacetic anhydride (7mL, 50.7mmol) was added ammonium nitrate (1.8g, 22.5mmol) in 0.3g each portion, keeping the reaction temperature between 25-3O0C. After the addition was complete, the mixture was poured into ice water and extracted with DCM (15mLx4). The extract was washed with water and the aqueous layer was extracted with DCM. The combined DCM extract was dried over MgSO4, filtered and concentrated to give a yellow green oil. The oil was triturated by hexane (cooled to 50C) to provide a solid which was filtered to provide 4b (0.72g, 44percent).
Reference:
[1] Journal of Organic Chemistry, 1987, vol. 52, # 13, p. 2714 - 2726
[2] Helvetica Chimica Acta, 1989, vol. 72, p. 556 - 569
[3] Patent: WO2009/154769, 2009, A1, . Location in patent: Page/Page column 37-38
[4] Zhurnal Obshchei Khimii, 1959, vol. 29, p. 535,538; engl. Ausg. S. 533
[5] Patent: WO2011/38572, 2011, A1, . Location in patent: Page/Page column 76
2
[ 181294-57-5 ]
[ 1121-13-7 ]
Reference:
[1] Journal of Organic Chemistry, 2004, vol. 69, # 24, p. 8382 - 8386
3
[ 1121-13-7 ]
[ 108511-97-3 ]
Reference:
[1] Journal of Organic Chemistry, 1987, vol. 52, # 13, p. 2714 - 2726
[2] Patent: WO2011/38572, 2011, A1, . Location in patent: Page/Page column 76
With ammonium nitrate; trifluoroacetic anhydride; at 25 - 30℃;
To the solution of 4a (Ig, 14.5mmol) in trifluoroacetic anhydride (7mL, 50.7mmol) was added ammonium nitrate (1.8g, 22.5mmol) in 0.3g each portion, keeping the reaction temperature between 25-3O0C. After the addition was complete, the mixture was poured into ice water and extracted with DCM (15mLx4). The extract was washed with water and the aqueous layer was extracted with DCM. The combined DCM extract was dried over MgSO4, filtered and concentrated to give a yellow green oil. The oil was triturated by hexane (cooled to 50C) to provide a solid which was filtered to provide 4b (0.72g, 44%).
With ammonium nitrate; trifluoroacetic anhydride; at 25 - 30℃;
Isoxazole (4.64 ml, 72.4 mmol) was dissolved in trifluoroacetic anhydride (30 ml) and ammonium nitrate (6.37 g, 80 mmol) was added in 0.5 g portions, keeping the reaction temperature between 25C~30C. Another batch of ammonium nitrate (3.6 g) was then added. About one third of the reaction solution was poured onto ice water, and extracted with dichloromethane (60 ml x4 ). The extracts were combined, washed with water (80 ml x 3), dried over anhydrous MgS04, and concentrated to yield the title compound as a yellow solid. 0.9 g.
With ammonium chloride; zinc; In water; at 0 - 5℃; for 2h;
4- Nitroisoxazole (may be prepared as described in Description 94; 850 mg, 7.45 mmol) was added to a solution of ammonium chloride (9169 mg, 171 mmol) in water (60 ml). The resultant suspension was cooled to 0°C, and zinc (4142 mg, 63.3 mmol) was added in portions whilst keeping the temperature below 5°C. After the addition, the mixture was stirred at 0-5°C for 2 hours. The reaction mixture was then filtered, and the filtrate was extracted with ethyl acetate (100 ml x 4). The organic phase was washed by water (100 ml x 2), dried over anhydrous MgS04, and concentrated to yield the title compound as a brown oil, 535 mg.
To a solution of 4b (200mg, 1.75mmol) in con. HCl (9mL) was added SnCl2.2H2O (1.98g, 8.77mmol). The mixture was stirred at rt for 1.5h, then adjusted by SaLNa2CO3 to pH=8~9 and filtered. The water phase was extracted with EA (30x4) and the combined extract was dried over anhydrous Na2SO4 and filtered. 5OmL of HClZEt2O solution was added to the filtrate and stirred for 30 min then evaporated to dryness to give 4c (125mg, 59%).
Step 1: lsoxazol-4-amine Hydrochloride (bbb-1); To a solution of NH4CI (317g, 5.93 mol) in water (1.4 L) was added <strong>[1121-13-7]4-nitroisoxazole</strong> (30.9 g, 0.26 mol; 95% purity; Reiter, L. A.; J. Org. Chem.; 1987; 52; 2714-2726). The resultant suspension was cooled to 0 C, and Zn (143 g, 2.20 mol) added in portions (0.5-1 g) to keep the temperature below 5C (an ice bath). After about 40% of Zn was added, the exotherm apparently subsided. After the Zn addition was completed, the mixture was stirred at ^0G for 10h, the cooling bath was removed, allowed to warm to ambient temperature, and ethyl acetate (1750 mL) was carefully added dropwise under vigorous stirring. Then the mixture was filtered to remove zinc salts (Caution: leftover Zn reacted exothermically on the filter), and the organic layer was separated. The aqueous layer was extracted with «thyl acetate. The combined organic layers were dried over MgSO4 and evaporated under reduced pressure to give an oily product (13.0 g), which was mixed with 4M HCI in dioxane (50 mL) and kept in a refrigerator overnight. The resultant precipitate was separated by filtration, washed with absolute ether (50 mL), and air-dried to give a light-brown solid in 48 yield % (15.1 g), which was used without further purification or characterization.