ethyl 2-cyano-2-formamidoacetate

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: A stirred solution of ethyl 2-cyano-2-(formylamino)acetate J. Org. Chem., 1979, 44, 3835; 0.47 g, 0.003 mol), acrylonitrile (1.2 ml, 0.018 mol) and trifluoroacetic acid (0.02 ml, 0.0003 mol) in 1,2-dichloroethane (4 ml) was heated under reflux for 3 days. The solvent was removed by evaporation under vacuum, the residue dissolved in dichloromethane (30 ml) and the resulting solution washed with saturated aqueous sodium bicarbonate solution (30 ml). The aqueous phase was washed with dichloromethane (30 ml) and the organic solutions then combined, dried (MgSO4) and evaporated under vacuum. Chromatography of the residue on silica gel (12 g), eluting with dichloromethane:methanol (100:1), followed by crystallisation from acetone: hexane, gave the title compound as a colourless solid (0.12 g, 21%), m.p. 114°-116° C. Found: C,56.89; H,4.75; N,22.08. C9H9N3O2 requires C,56.54; H,4.75; N,21.98%. under reflux for 3 days The solvent was removed by evaporation under vacuum the residue dissolved in dichloromethane (30 ml) the resulting solution washed with saturated aqueous sodium bicarbonate solution (30 ml) The aqueous phase was washed with dichloromethane (30 ml) dried (MgSO4) evaporated under vacuum Chromatography of the residue on silica gel (12 g), eluting with dichloromethane:methanol (100:1) followed by crystallisation from acetone

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

実験手順: A stirred solution of ethyl 2-cyano-2-(formyl-amino)acetate (J. Org. Chem., 1979, 44, 3835; 0.47 g, 0.003 mol), acrylonitrile (1.2 ml, 0.018 mol) and tri-fluoroacetic acid (0.02 ml, 0.0003 mol) in 1,2-dichloroethane (4 ml) was heated under reflux for 3 days. The solvent was removed by evaporation under vacuum, the residue dissolved in dichloromethane (30 ml) and the resulting solution washed with saturated aqueous sodium bicarbonate solution (30 ml). The aqueous phase was washed with dichloromethane (30 ml) and the organic solutions then combined, dried (MgSO4) and evaporated under vacuum. Chromatography of the residue on silica gel (12 g), eluting with dichloromethane:methanol (100:1), followed by crystallization from acetone:hexane, gave the title compound as a colourless solid (0.12 g, 21%), m.p. 114-116° C. under reflux for 3 days The solvent was removed by evaporation under vacuum the residue dissolved in dichloromethane (30 ml) the resulting solution washed with saturated aqueous sodium bicarbonate solution (30 ml) The aqueous phase was washed with dichloromethane (30 ml) dried (MgSO4) evaporated under vacuum Chromatography of the residue on silica gel (12 g), eluting with dichloromethane:methanol (100:1) followed by crystallization from acetone

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

実験手順: Under a nitrogen atmosphere (N2), HCOOH (2.44 g, 53 mmol) was added to Ac2O (6.48 g, 63.6 mmol) at 0° C. After it was allowed to warm to ambient temperature the reaction was heated at 50° C. for 15 hr. It was allowed to cool to ambient temperature. This mixed acid anhydride was then added dropwise to a solution of ethyl 2-amino-2-cyanoacetate (128 mg, 1 mmol) in dry THF (5 mL) at 0° C. After the cooling bath was removed, the reaction was maintained at ambient temperature for additional 1 hr. The reaction mixture was concentrated and purified by silica gel column chromatography (5:1 PE/EtOAc) to afford ethyl 2-cyano-2-formamidoacetate (110 mg, 70%) as a white solid. was heated at 50° C. for 15 hr to cool to ambient temperature After the cooling bath was removed the reaction was maintained at ambient temperature for additional 1 hr The reaction mixture was concentrated purified by silica gel column chromatography (5:1 PE/EtOAc)

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

実験手順: Under a nitrogen atmosphere (N2), HCOOH (2.44 g, 53 mmol) was added to Ac2O (6.48 g, 63.6 mmol) at 0° C. After it was allowed to warm to ambient temperature the reaction was heated at 50° C. for 15 hr. It was allowed to cool to ambient temperature. This mixed acid anhydride was then added dropwise to a solution of ethyl 2-amino-2-cyanoacetate (128 mg, 1 mmol) in dry THF (5 mL) at 0° C. After the cooling bath was removed, the reaction was maintained at ambient temperature for additional 1 hr. The reaction mixture was concentrated and purified by silica gel column chromatography (5:1 PE/EtOAc) to afford ethyl 2-cyano-2-formamidoacetate (110 mg, 70%) as a white solid. was heated at 50° C. for 15 hr to cool to ambient temperature After the cooling bath was removed the reaction was maintained at ambient temperature for additional 1 hr The reaction mixture was concentrated purified by silica gel column chromatography (5:1 PE/EtOAc)

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

実験手順: A stirred solution of ethyl 2-cyano-2-(formylamino)acetate J. Org. Chem., 1979, 44, 3835; 0.47 g, 0.003 mol), acrylonitrile (1.2 ml, 0.018 mol) and trifluoroacetic acid (0.02 ml, 0.0003 mol) in 1,2-dichloroethane (4 ml) was heated under reflux for 3 days. The solvent was removed by evaporation under vacuum, the residue dissolved in dichloromethane (30 ml) and the resulting solution washed with saturated aqueous sodium bicarbonate solution (30 ml). The aqueous phase was washed with dichloromethane (30 ml) and the organic solutions then combined, dried (MgSO4) and evaporated under vacuum. Chromatography of the residue on silica gel (12 g), eluting with dichloromethane:methanol (100:1), followed by crystallisation from acetone: hexane, gave the title compound as a colourless solid (0.12 g, 21%), m.p. 114°-116° C. Found: C,56.89; H,4.75; N,22.08. C9H9N3O2 requires C,56.54; H,4.75; N,21.98%. under reflux for 3 days The solvent was removed by evaporation under vacuum the residue dissolved in dichloromethane (30 ml) the resulting solution washed with saturated aqueous sodium bicarbonate solution (30 ml) The aqueous phase was washed with dichloromethane (30 ml) dried (MgSO4) evaporated under vacuum Chromatography of the residue on silica gel (12 g), eluting with dichloromethane:methanol (100:1) followed by crystallisation from acetone

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

実験手順: Under N2, HCOOH (2.44 g, 53 mmol) was added to Ac2O (6.48 g, 63.6 mmol) at 0° C. After it was allowed to warm to ambient temperature the reaction was heated at 50° C. for 15 hr. It was allowed to cool to ambient temperature. This mixed acid anhydride was then added dropwise to a solution of ethyl 2-amino-2-cyanoacetate (128 mg, 1 mmol) in dry THF (5 mL) at 0° C. After the cooling bath was removed, the reaction was maintained at ambient temperature for additional 1 hr. The reaction mixture was concentrated and purified by silica gel column chromatography (5:1 PE/EtOAc) to afford ethyl 2-cyano-2-formamidoacetate (110 mg, 70%) as a white solid. was heated at 50° C. for 15 hr to cool to ambient temperature After the cooling bath was removed the reaction was maintained at ambient temperature for additional 1 hr The reaction mixture was concentrated purified by silica gel column chromatography (5:1 PE/EtOAc)

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

実験手順: A stirred solution of ethyl 2-cyano-2-(formylamino)acetate (J. Org. Chem., 1979, 44, 3835; 0.47 g, 0.003 mol), acrylonitrile (1.2 ml, 0.018 mol) and tri-fluoroacetic acid (0.02 ml, 0.0003 mol) in 1,2-dichloroethane (4 ml) was heated under reflux for 3 days. The solvent was removed by evaporation under vacuum, the residue dissolved in dichloromethane (30 ml) and the resulting solution washed with saturated aqueous sodium bicarbonate solution (30 ml). The aqueous phase was washed with dichloromethane (30 ml) and the organic solutions then combined, dried (MgSO4) and evaporated under vacuum. Chromatography of the residue on silica gel (12 g), eluting with dichloromethane:methanol (100:1), followed by crystallization from acetone:hexane, gave the title compound as a colourless solid (0.12 g, 21%), m.p. 114-116° C. under reflux for 3 days The solvent was removed by evaporation under vacuum the residue dissolved in dichloromethane (30 ml) the resulting solution washed with saturated aqueous sodium bicarbonate solution (30 ml) The aqueous phase was washed with dichloromethane (30 ml) dried (MgSO4) evaporated under vacuum Chromatography of the residue on silica gel (12 g), eluting with dichloromethane:methanol (100:1) followed by crystallization from acetone

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

実験手順: Under a nitrogen atmosphere (N2), HCOOH (2.44 g, 53 mmol) was added to Ac2O (6.48 g, 63.6 mmol) at 0° C. After it was allowed to warm to ambient temperature the reaction was heated at 50° C. for 15 hr. It was allowed to cool to ambient temperature. This mixed acid anhydride was then added dropwise to a solution of ethyl 2-amino-2-cyanoacetate (128 mg, 1 mmol) in dry THF (5 mL) at 0° C. After the cooling bath was removed, the reaction was maintained at ambient temperature for additional 1 hr. The reaction mixture was concentrated and purified by silica gel column chromatography (5:1 PE/EtOAc) to afford ethyl 2-cyano-2-formamidoacetate (110 mg, 70%) as a white solid. was heated at 50° C. for 15 hr to cool to ambient temperature After the cooling bath was removed the reaction was maintained at ambient temperature for additional 1 hr The reaction mixture was concentrated purified by silica gel column chromatography (5:1 PE/EtOAc)

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

実験手順: Under N2, HCOOH (2.44 g, 53 mmol) was added to Ac2O (6.48 g, 63.6 mmol) at 0° C. After it was allowed to warm to ambient temperature the reaction was heated at 50° C. for 15 hr. It was allowed to cool to ambient temperature. This mixed acid anhydride was then added dropwise to a solution of ethyl 2-amino-2-cyanoacetate (128 mg, 1 mmol) in dry THF (5 mL) at 0° C. After the cooling bath was removed, the reaction was maintained at ambient temperature for additional 1 hr. The reaction mixture was concentrated and purified by silica gel column chromatography (5:1 PE/EtOAc) to afford ethyl 2-cyano-2-formamidoacetate (110 mg, 70%) as a white solid. was heated at 50° C. for 15 hr to cool to ambient temperature After the cooling bath was removed the reaction was maintained at ambient temperature for additional 1 hr The reaction mixture was concentrated purified by silica gel column chromatography (5:1 PE/EtOAc)

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

実験手順: A solution of ethyl 2-cyano-2-formamidoacetate (480 mg, 3.07 mmol) and Lawesson's reagent (746 mg, 1.84 mmol) in toluene (5 mL) was heated up to 80° C. for overnight. The reaction was then diluted with sodium carbonate aqueous solution (20 mL) and methylene chloride (50 mL). Organic phase was washed with brine (20 mL), dried over sodium sulfate and concentrated. Purified with silica gel chromatography to give a solid material of ethyl 5-aminothiazole-4-carboxylate (120 mg). 1H NMR (400 MHz, CDCl3) δ 7.86 (s, 1H), 5.98 (s, br, 2H), 4.38 (q, 2H), 1.41 (t, 3H). MS m/z 173.2 (M+H)+. Organic phase was washed with brine (20 mL) dried over sodium sulfate concentrated Purified with silica gel chromatography