1-phenylpyrrolidine-2,3-dione

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

Procedure: A solution of the product of Example 61 and chiral 1-amino-2-methoxymethylpyrrolidine (SAMP or RAMP; 1 equiv) in benzene is refluxed under Dean-Stark conditions for 20 h. After cooling, Et2O is added and the mixture is washed with water. The organic layer is dried (MgO4) and evaporated to give a residue which is chromatographed on silica gel to give the title compound. After cooling the mixture is washed with water The organic layer is dried (MgO4) evaporated to give a residue which is chromatographed on silica gel

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

Procedure: A solution of the product of Example 61 and chiral 1-amino-2-methoxymethylpyrrolidine (SAMP or RAMP; 1 equiv) in benzene is refluxed under Dean-Stark conditions for 20 h. After cooling, Et2O is added and the mixture is washed with water. The organic layer is dried (MgO4) and evaporated to give a residue which is chromatographed on silica gel to give the title compound. After cooling the mixture is washed with water The organic layer is dried (MgO4) evaporated to give a residue which is chromatographed on silica gel

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

Procedure: A solution of the product of Example 61 in THF is added to a solution of lithium di-iso-propylamide (LDA) in THF at -78° C. After 2 h at -78° C. a solution of ethyl bromoacetate is added and the reaction is allowed to warm to room temperature. After an aqueous workup the crude product is chromatographed on silica gel to give the title compound. After an aqueous workup the crude product is chromatographed on silica gel

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

Procedure: According to the procedure of Southwick [J. Org. Chem. 21, 1087 (1956)] the ethyl ester pyrrolidinone of Example S (1.0 g, 4.0 mmol) was suspended in 75 ml of 20% HCl/H2O and refluxed for 3.5 h The reaction was cooled and filtered and the filtrate was extracted with CHCl3 (4×150 ml). Concentration of the combined extracts gave an off-white solid (358 mg). 'NMR(300 MHZ, CDCl3) δ2.92 (t, 2H), 4.17 (t, 2H), 7.32 (t, 1H), 7.98 (t, 2H), 7.84 (d, 2H). refluxed for 3.5 h The reaction was cooled filtered the filtrate was extracted with CHCl3 (4×150 ml)

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

Procedure: According to the procedure of Southwick [J. Org. Chem. 21, 1087 (1956)] the ethyl ester pyrrolidinone of Example S (1.0 g, 4.0 mmol) was suspended in 75 ml of 20% HCl/H2O and refluxed for 3.5 h The reaction was cooled and filtered and the filtrate was extracted with CHCl3 (4×150 ml). Concentration of the combined extracts gave an off-white solid (358 mg). 'NMR(300 MHZ, CDCl3) δ2.92 (t, 2H), 4.17 (t, 2H), 7.32 (t, 1H), 7.98 (t, 2H), 7.84 (d, 2H). refluxed for 3.5 h The reaction was cooled filtered the filtrate was extracted with CHCl3 (4×150 ml)

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

Procedure: A solution of the product of Example 61 and chiral 1-amino-2-methoxymethylpyrrolidine (SAMP or RAMP; 1 equiv) in benzene is refluxed under Dean-Stark conditions for 20 h After cooling, Et2O is added and the mixture is washed with water. The organic layer is dried (MgO4), and evaporated to give a residue which is chromatographed on silica gel to give the title compound. After cooling the mixture is washed with water The organic layer is dried (MgO4) evaporated to give a residue which is chromatographed on silica gel

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

Procedure: A solution of the product of Example 61 in THF is added to a solution of lithium di-iso-propylamide (LDA) in THF at -78° C. After 2 h at -78° C. a solution of ethyl bromoacetate is added and the reaction is allowed to warm to room temperature. After an aqueous workup the crude product is chromatographed on silica gel to give the title compound. After an aqueous workup the crude product is chromatographed on silica gel

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

Procedure: According to the procedure of Southwick [J. Org. Chem. 21, 1087 (1956)]the ethyl ester pyrrolidinone of Example S (1.0 g, 4.0 mmol) was suspended in 75 ml of 20% HCl/H2O and refluxed for 3.5 h The reaction was cooled and filtered and the filtrate was extracted with CHCl3 (4×150 ml). Concentration of the combined extracts gave an off-white solid (358 mg). 'NMR(300 MHZ, CDCl3) δ2.92 (t, 2H), 4.17 (t, 2H), 7.32 (t, 1H), 7.98 (t, 2H), 7.84 (d, 2H). refluxed for 3.5 h The reaction was cooled filtered the filtrate was extracted with CHCl3 (4×150 ml)

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

Procedure: A solution of the product of Example 61 and chiral 1-amino-2-methoxymethylpyrrolidine (SAMP or RAMP; 1 equiv) in benzene is refluxed under Dean-Stark conditions for 20 h. After cooling, Et2O is added and the mixture is washed with water. The organic layer is dried (MgO4) and evaporated to give a residue which is chromatographed on silica gel to give the title compound. After cooling the mixture is washed with water The organic layer is dried (MgO4) evaporated to give a residue which is chromatographed on silica gel

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

Procedure: A solution of the product of Example 61 in THF is added to a solution of lithium di-iso-propylamide (LDA) in THF at -78° C. After 2 h at -78° C. a solution of ethyl bromoacetate is added and the reaction is allowed to warm to room temperature. After an aqueous workup the crude product is chromatographed on silica gel to give the title compound. After an aqueous workup the crude product is chromatographed on silica gel

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

Procedure: According to the procedure of Southwick [J. Org. Chem. 21, 1087 (1956)] the ethyl ester pyrrolidinone of Example S (1.0 g, 4.0 mmol) was suspended in 75 ml of 20% HCl/H2O and refluxed for 3.5 h The reaction was cooled and filtered and the filtrate was extracted with CHCl3 (4×150 ml). Concentration of the combined extracts gave an off-white solid (358 mg). 'NMR(300 MHZ, CDCl3) δ2.92 (t, 2H), 4.17 (t, 2H), 7.32 (t, 1H), 7.98 (t, 2H), 7.84 (d, 2H). refluxed for 3.5 h The reaction was cooled filtered the filtrate was extracted with CHCl3 (4×150 ml)