4,4-dimethyl-3-oxopentanenitrile

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sulfuric acid (concentrated, 15.7 mL, 295.7 mmol) was carefully added drop-wise to cold EtOH (600 mL) with stirring. To this, 3-hydrazinobenzoic acid (45 g, 295.7 mmol) and 4,4-dimethyl-3-oxopentanenitrile (40.7 g, 325.3 mmol) were added and then the mixture was heated at 90° C. for 48 h. Most of the solvent was evaporated at reduced pressure, and the residual mixture was diluted with ethyl acetate. The resulting mixture was washed with ice cold 2M NaOH followed by brine, and dried (Na2SO4). The solution was filtered through a bed of silica gel, washing with more ethyl acetate. Evaporation of ethyl acetate and treatment of the residue with dichloromethane/hexanes gave the product as an off-white crystalline solid (61 g, 71%). MS m/z 288.2 (M+H)+; calcd. mass 287. Retention time (LC-MS): 2.99 min. 1H-NMR (DMSO-d6): δ 8.16 (m 1H); 7.88 (m, 2H); 7.60 (t, 1H); 5.40 (s, 1H); 5.32 (s, 2H); 4.36 (q, 2H); 1.34 (t, 3H); 1.21 (s, 9H). Most of the solvent was evaporated at reduced pressure the residual mixture was diluted with ethyl acetate The resulting mixture was washed with ice cold 2M NaOH dried (Na2SO4) The solution was filtered through a bed of silica gel washing with more ethyl acetate Evaporation of ethyl acetate and treatment of the residue with dichloromethane/hexanes

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Pivaloylacetonitrile (1.00 g, 7.99 mmol) was dissolved in carbon tetrachloride (15 mL). N-Bromosuccinimide (1.42 g, 7.99 mmol) was added, and the mixture was refluxed for 15 minutes. After cooling, the insoluble matter was filtered off, and the residue obtained by evaporation of the filtrate under reduced pressure was purified by chromatography on silica gel (n-hexane:ethyl acetate=4:1) to give the title compound (1.43 g, 87.9%) as a yellowish brown oil. the mixture was refluxed for 15 minutes After cooling the insoluble matter was filtered off the residue obtained by evaporation of the filtrate under reduced pressure was purified by chromatography on silica gel (n-hexane:ethyl acetate=4:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Isopropanol 800 ml was added to pivaloylacetonitrile 600 g and heating and stirring were applied. Hydrazine hydrate 288 g was dropped thereto and heating and stirring were applied for 3 hours. After finishing the reaction, isopropanol 400 ml was distilled off under reduced pressure. Ethyl acetate 2000 ml and a saturated salt aqueous solution were added to a residue and stirring was applied. After leaving for standing for a while, an aqueous layer was removed and an ethyl acetate layer was washed twice with the saturated salt aqueous solution, followed by drying an ethyl acetate solution over magnesium sulfate anhydrous. This ethyl acetate solution was concentrated under reduced pressure and then n-hexane 2000 ml was added to a residue to precipitate crystal. This crystal was filtered off and dried, whereby 3-amino-5-t-butylpyrazole (Compound (A)) 643 g (96.2%) was obtained. The melting point was 74.0 to 75.0° C. heating heating stirring was distilled off under reduced pressure Ethyl acetate 2000 ml and a saturated salt aqueous solution were added to a residue stirring After leaving an aqueous layer was removed an ethyl acetate layer was washed twice with the saturated salt aqueous solution by drying an ethyl acetate solution over magnesium sulfate anhydrous This ethyl acetate solution was concentrated under reduced pressure n-hexane 2000 ml was added to a residue to precipitate crystal This crystal was filtered off dried

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