Chloride → 3-Phenyl-2-(phenylamino)propanoic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of (S)-2-amino-3-phenylpropanoic acid (1.52 g, 9.12 mmol) in a DMF/H2O mixture (10/1, 16.5 mL) maintained under nitrogen flowstream, iodobenzene (1.00 mL, 9.12 mmol), dichlorobis(tri-o-tolylphosphine)palladium(II) (357 mg, 0.42 mmol) CuI (86.4 mg, 0.42 mmol), K2CO3 (1.21 g, 9.12 mmol), rimethylbenzylammonium chloride (286 mg, 1.51 mmol) and triethylamine (TEA) (2.50 mL, 18.0 mmol) are added and the mixture stirred for 24 hours at 100° C. under nitrogen flowstream (LC-MS monitoring: complete conversion). The reaction mixture is partitioned between EtOAc and water; 1N HCl is added until pH=1 and the organic layer is separated, washed with brine and dried over Na2SO4. The resulting crude is purified by flash chromatography (DCM/MeOH=99/1) and 1.21 g of I21 is obtained (56% yield).

Provenance & Evidence