1-prop-2-ynylpyrrolidine-2,5-dione

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the example given in Example 1B, 19.1 g. (0.15 mole) of N-propargylsuccinimide was caused to react with 6.3 g. of paraformaldehyde and 14.2 g. (0.2 mole) of pyrrolidine in 100 ml. of dioxane in the presence of a trace of cuprous chloride. The reaction was refluxed for 5 hrs. and allowed to stand overnight. After filtration of the reaction mixture and removal of the solvent from the filtrate, the residual oil was distilled to give N-[4-(1-pyrrolidinyl)-2-butynyl]-succinimide boiling at 155° C. at 0.04 mm. This product solidified, and after recrystallization from ether, melted at 93.0 to 94.0° C. (corr.). to react with 6.3 g The reaction was refluxed for 5 hrs After filtration of the reaction mixture and removal of the solvent from the filtrate the residual oil was distilled

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4.26 g (15 mmol) triflate (6.1b), 2.47 g (18 mmol) of 1-prop-2-ynyl-pyrrolidine-2,5-dione (7.4), 0.067 g (0.3 mmol) of [(C6H5)3P]2PdCl2, 0.143 g (0.75 mmol) CuI, 0.32 g (0.75 mmol) of 1,4-bis(diphenyl-phosphino)butane and 7 ml (50.5 mmol) of TEA in 40 ml DMF under nitrogen at 100° C. for 3 h. The inorganic salts are removed and DMF is evaporated. The residue is treated with water, extracted 3×50 ml of EtOAc, the collected organic phase is evaporated and purified by flash chromatography (toluene-MeOH 9:1). The desired intermediate 4.19 is 1.9 g (44%) of 4-[3-(2,5-dioxo-pyrrolidin-1-yl)-prop-1-ynyl]-3-methoxy-benzaldehyde, as a dark yellow solid. (M+H)+=272, Rt=2.15 min (A), purity: 98.9%. The inorganic salts are removed DMF is evaporated The residue is treated with water extracted 3×50 ml of EtOAc the collected organic phase is evaporated purified by flash chromatography (toluene-MeOH 9:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the example given in Example 1B, 19.1 g. (0.15 mole) of N-propargylsuccinimide was caused to react with 6.3 g. of paraformaldehyde and 14.2 g. (0.2 mole) of pyrrolidine in 100 ml. of dioxane in the presence of a trace of cuprous chloride. The reaction was refluxed for 5 hrs. and allowed to stand overnight. After filtration of the reaction mixture and removal of the solvent from the filtrate, the residual oil was distilled to give N-[4-(1-pyrrolidinyl)-2-butynyl]-succinimide boiling at 155° C. at 0.04 mm. This product solidified, and after recrystallization from ether, melted at 93.0 to 94.0° C. (corr.). to react with 6.3 g The reaction was refluxed for 5 hrs After filtration of the reaction mixture and removal of the solvent from the filtrate the residual oil was distilled