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With titanium tetrachloride; zinc In tetrahydrofuran at 20℃; for 0.0833333 h; Inert atmosphere
General procedure: TiCl4 (0.7 mL, 6 mmol)was added to a stirred suspension of Zn powder (0.78 g, 12 mmol) in freshlydistilled anhydrous THF (15 mL) at room temperature (rt) under a dry N2atmosphere. After completion of the addition, the mixture was refluxed for 2 h.The suspension of the low-valent titanium reagent thus-formed was cooled tort. A solution of isatin or its derivatives 1 or 3 (2 mmol) in THF (10 mL) wasadded dropwise. The mixture was stirred at room temperature for about 5 minunder N2. After this period, the thin layer chromatography (TLC) analysis of themixture showed the reaction completed. The reaction mixture was quenchedwith 3percent HCl (15 mL) and extracted with CHCl3 (3 50 mL). The combinedextracts were washed with water (3 50 mL) and dried over anhydrousNa2SO4. After evaporation of the solvent under reduced pressure, the crudeproduct was purified by column chromatography (petroleum ether/ethylacetate = 5:1) to give the pure products 2 or 4.
72%
Stage #1: With hydrazine hydrate In water at 140℃; for 6 h; Stage #2: With hydrogenchloride In water at 20℃; for 12 h;
General procedure: Isatins (1a–j, 3.0 g), hydrazine hydrate (80percent, 13 mL) and water (13 mL) were added to a flask equipped with a thermometer with vigorous stirring. The reaction mixture was kept at 140 °C in an oil bath for 6 h before being cooled to r.t., when hydrochloric acid (2.0 mol L?1) was added to bring the pH to pH 2. The reaction mixture was stirred at r.t. for 12 h. Compounds 2a–j were obtained by filtering under vacuum and recrystallisation from absolute ethanol.
Reference：
[1] Tetrahedron Letters, 2014, vol. 55, # 14, p. 2238 - 2242
[2] Tetrahedron Letters, 2000, vol. 41, # 47, p. 9089 - 9093
[3] Journal of Chemical Research, 2017, vol. 41, # 9, p. 537 - 540
[4] Patent: WO2017/199265, 2017, A1, . Location in patent: Paragraph 000170
2
[ 400629-31-4 ]
[ 320734-35-8 ]
Yield
Reaction Conditions
Operation in experiment
27%
With sulfuric acid; zinc In ethanol; water at 20 - 70℃; for 1 h;
To a freshly prepared mixture of 1-bromo-2-nitro-benzene acetic acid (1.98 g, 7.61 mmol) in EtOH (20 mL) and 9M H2SO4 (20 mL) at 50° C. was added Zn dust( 2.00 g, 30.6 mmol) at ambient temperature. The reaction was stirred for 30 minutes at ambient temperature and then at 70° C. for 30 minutes. The reaction was cooled to ambient temperature and poured into H2O (100 mL) and estracted with EtOAc (2.x.50 mL). The combined organic Layers were dried (Na2SO4), filtered and evaporated to give a crude brown residue. Chromatography on silica gel eluting with a gradient EtOAc-hexane system (1:10 to 1:1) gave the intermediate title compound (0.43 g, 27percent) as a light brown solid. Analysis Theory: C, 45.31; H, 2.85; N, 6.60 Found: C, 45.01; H, 2.55; N, 6.42
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