甲基 2-氰基丁酸甲酯

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To (±)-2-bromobutyric acid(167.01 g) was added water (150 ml). Sodium carbonate (54.05 g) was added slowly over an hour and dissolved therein. A solution of potassium cyanide (68.55 g) dissolved in water (150 ml) was added, and heated to about 50° C. Accordingly as the reaction progressed, the temperature of the reaction solution rose to 80° C. The reaction solution was stirred at 80°~90° C. for an hour, cooled to room temperature, and neutralized with conc. hydrochloric acid (120 ml). Afterwards, the such neutralized solution was concentrated under reduced pressure, and ethyl alcohol (500 ml) was added to the residue. The obtained ethanolic solution was concentrated under reduced pressure again. To the residue was added ethyl alcohol (700 ml), followed by filtration. After conc. sulfuric acid (3 ml) was added to the filtrate, the solution was refluxed for 5 hours and distilled to remove about 300 ml of ethyl alcohol. The solution was concentrated under reduced prrssure, and the residue was added to sodium carbonate saturated solution(400 ml). After extraction with ether (500 ml), the separated organic layer was washed with a 10% saline solution (500 ml) and a saturated saline solution(300 ml), dried over anhydrous magnesium sulfate, filtered and then concentrated. The residue was distilled under reduced pressure to give the colorless above-indicated compound(49.90 g). dissolved was added rose to 80° C cooled to room temperature Afterwards, the such neutralized solution was concentrated under reduced pressure, and ethyl alcohol (500 ml) was added to the residue The obtained ethanolic solution was concentrated under reduced pressure again To the residue was added ethyl alcohol (700 ml) followed by filtration After conc. sulfuric acid (3 ml) was added to the filtrate the solution was refluxed for 5 hours distilled to remove about 300 ml of ethyl alcohol The solution was concentrated under reduced prrssure the residue was added to sodium carbonate saturated solution(400 ml) After extraction with ether (500 ml) the separated organic layer was washed with a 10% saline solution (500 ml) a saturated saline solution(300 ml), dried over anhydrous magnesium sulfate filtered concentrated The residue was distilled under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a slurry of Raney-Ni (1.9 g, 50% in H2O, rinsed 3 times with EtOH before use) in EtOH (20 mL) was added methyl 2-cyanobutanoate (200 mg, 1.57 mmol). The resulting mixture was stirred under a hydrogen atmosphere at room temperature for 20 hours. The liquid was then carefully decanted into another flask and the metal was washed twice with EtOH. The combined EtOH solution was concentrated in vacuo to give the title compound in 200 mg, which was used in the subsequent step without further purification. The liquid was then carefully decanted into another flask the metal was washed twice with EtOH The combined EtOH solution was concentrated in vacuo

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of methyl 2-cyanoacetate (2.0 mL, 22.61 mmol., Acros) and DBU (3.4 mL, 22.61 mmol) in DMF (22 mL) was added iodoethane (2.0 mL, 24.90 mmol) dropwise at 0° C. The resulting mixture was heated to 70° C. for 20 hours. After cooling to room temperature, H2O (150 mL) and EtOAc (150 mL) were added. The layers were separated and the aqueous layer was extracted twice with EtOAc. The combined organic layers were dried over MgSO4, concentrated, and purified by flash chromatography (0-30% EtOAc/hexanes) to give the title compound in 300 mg. 1H NMR (CDCl3, 200 MHz): δ=3.82 (s, 3H), 3.48 (dd, 1H, J=5.9 Hz and 6.8 Hz), 2.08-1.92 (m, 2H), 1.12 (t, 3H, J=7.3 Hz). After cooling to room temperature The layers were separated the aqueous layer was extracted twice with EtOAc The combined organic layers were dried over MgSO4 concentrated purified by flash chromatography (0-30% EtOAc/hexanes)