6-IODO-3 H-ISOBENZOFURAN-1-ONE

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

Procedure: The 6-iodophthalide was prepared in 23% yield via diazotization of 6-aminophthalide and subsequent treatment of the diazonium salt with potassium iodide according to the method of Tassman (Rec. Trav. Chim. Pays-Bas, 46, 653).

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

Procedure: The 6-iodophthalide was prepared in 23% yield via diazotization of 6-aminophthalide and subsequent treatment of the diazonium salt with potassium iodide according to the method of Tassman (Rec. Trav. Chim. Pays-Bas, 46, 653).

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

Procedure: A solution of 6-iodophthalide (1.0 g, 3.85 mmol), (S)-3-methylphenylalanine.HCl (0.83 g, 3.85 mmol) K2CO3 (0.53 g, 3.85 mmol), CuI (73 mg, 0.38 mmol), TEBA (0.32 g, 1.3 mmol), tri-o-tolylphosphine (0.23 g, 0.77 mmol), Pd(OAc)2 (86 mg, 0.38 mmol), triethylamine (2.14 mL, 15.38 mmol) and water (1.2 mL) in DMF (12 mL) is heated to 100° C. for 12 h. After cooling, the solution is diluted with EtOAc, and washed with 1 N HCl (100 mL), sat'd LiCl (50 mL) and water (100 mL), evaporated and chromatographed (2% MeOH/CH2Cl2, 0 to 0.05% acetic acid) to yield (S)-6-[(1-carboxy-2-(3-methylphenyl)-ethylamino]-phthalide, as a light brown foam. After cooling washed with 1 N HCl (100 mL), sat'd LiCl (50 mL) and water (100 mL) evaporated chromatographed (2% MeOH/CH2Cl2, 0 to 0.05% acetic acid)

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

Procedure: A solution of 6-iodophthalide (1.0 g, 3.85 mmol), (S)-3-methylphenylalanine.HCl (0.83 g, 3.85 mmol) K2CO3 (0.53 g, 3.85 mmol), CuI (73 mg, 0.38 mmol), TEBA (0.32 g, 1.3 mmol), tri-o-tolylphosphine (0.23 g, 0.77 mmol), Pd(OAc)2 (86 mg, 0.38 mmol), triethylamine (2.14 mL, 15.38 mmol) and water (1.2 mL) in DMF (12 mL) is heated to 100° C. for 12 h. After cooling, the solution is diluted with EtOAc, and washed with 1 N HCl (100 mL), sat'd LiCl (50 mL) and water (100 mL), evaporated and chromatographed (2% MeOH/CH2Cl2, 0 to 0.05% acetic acid) to yield (S)-6-[(1-carboxy-2-(3-methylphenyl)-ethylamino]-phthalide, as a light brown foam. After cooling washed with 1 N HCl (100 mL), sat'd LiCl (50 mL) and water (100 mL) evaporated chromatographed (2% MeOH/CH2Cl2, 0 to 0.05% acetic acid)

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

Procedure: A solution of 6-iodophthalide (1.0 g, 3.85 mmol), (S)-3-methylphenylalanine.HCl (0.83 g, 3.85 mmol) K2CO3 (0.53 g, 3.85 mmol), CuI (73 mg, 0.38 mmol), TEBA (0.32 g, 1.3 mmol), tri-o-tolylphosphine (0.23 g, 0.77 mmol), Pd(OAc)2 (86 mg, 0.38 mmol), triethylamine (2.14 mL, 15.38 mmol) and water (1.2 mL) in DMF (12 mL) is heated to 100° C. for 12 h. After cooling, the solution is diluted with EtOAc, and washed with 1 N HCl (100 mL), sat'd LiCl (50 mL) and water (100 mL), evaporated and chromatographed (2% MeOH/CH2Cl2, 0 to 0.05% acetic acid) to yield (S)-6-[(1-carboxy-2-(3-methylphenyl)-ethylamino]-phthalide, as a light brown foam. After cooling washed with 1 N HCl (100 mL), sat'd LiCl (50 mL) and water (100 mL) evaporated chromatographed (2% MeOH/CH2Cl2, 0 to 0.05% acetic acid)

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

Procedure: The 6-iodophthalide was prepared in 23% yield via diazotization of 6-aminophthalide and subsequent treatment of the diazonium salt with potassium iodide according to the method of Tassman (Rec. Trav. Chim. Pays-Bas, 46, 653).