ethyl 3-chloro-2-cyanobenzoate

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:; See reaction.notes.procedure_details.

実験手順: Lithium hydroxide (44.0 mg, 1.049 mmol) was added to a solution of the ethyl 3-chloro-2-cyanobenzoate (200 mg, 0.954 mmol) in 1,4-dioxane (2 mL) and water (2.000 mL) and the reaction was stirred at room temperature for 18 h. LCMS: No SM remains. The solvent was evaporated and the residue was dissolved in water. This was washed with Et2O and then carefully acidified (2M HCl) to pH ˜1. The resulting pink solid was collected, washed with water and dried invacuo to afford desired product in 153 mg). The solvent was evaporated the residue was dissolved in water This was washed with Et2O The resulting pink solid was collected washed with water dried invacuo

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Hydrochloric acid (4.57 mL, 150 mmol) was added to a suspension of the ethyl 2-amino-3-chlorobenzoate (1.5 g, 7.51 mmol) in water (40 mL) and the mixture was cooled to 0° C. [note: compound did not go into solution] To this cooled mixture was added sodium nitrite (0.518 g, 7.51 mmol) portionwise keeping the temperature below 5° C. After addition the reaction was stirred for 40 mins. A small amount of toluene (3 ml) was added to aid dissolution. The mixture was then basified to pH˜6 by the addition of Na2CO3. In a separate flask potassium cyanide (2.202 g, 33.8 mmol) was added portionwise to a biphasic solution of copper(II) sulfate (1.439 g, 9.02 mmol) in water (15 mL) and toluene (15 mL) at 0° C. [note: exothermic reaction] After addition the now brown mixture was heated to 60° C. To this was added the diazonium salt dropwise via a dropping funnel (mixture kept at 0° C. during addition). After addition the reaction was stirred at 70° C. for 1 hr. The reaction was cooled and EtOAc was added. The organic layer was collected, dried (Na2SO4) and the solvent evaporated to afford a crude dark brown oil. LCMS: 2 major peaks+1 minor peak present. (One major peak corresponds to the SM—no mass ion observed). The crude material was purified by chromatography, SP4, 100 g SNAP, 0 to 100% EtOAc/i-Hexane (fasted eluting first). The desired product was identified in 398 mg. the temperature below 5° C After addition the reaction [note: exothermic reaction] After addition the now brown mixture was heated to 60° C (mixture kept at 0° C. during addition) After addition the reaction was stirred at 70° C. for 1 hr The reaction was cooled The organic layer was collected dried (Na2SO4) the solvent evaporated to afford a crude dark brown oil The crude material was purified by chromatography, SP4, 100 g SNAP, 0 to 100% EtOAc/i-Hexane (fasted eluting first)