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.
