Iodine → Methyl 2-((tert-butoxycarbonyl)amino)-3-iodopropanoate

Participants

Reaction Steps

To a three necked flask charged with zinc dust (2.23 g, 34.1 mmol) under an N2 atmosphere DMF (13 mL) was added. The suspension was efficiently stirred and I2 (0.20 g, 0.80 mmol) was added. ((S)-2-[(tert-Butoxycarbonyl)amino]-3-iodopropionic acid methyl ester (4.50 g, 13.7 mmol) was added in one portion, and immediately after more I2 (0.20 g, 0.80 mmol) and the stirring was continued for 2 h. Negishi coupling was then effected by addition in direct sequence of: Pd2 dba3 (315 mg, 0.34 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (279 mg, 0.68 mmol), and 1-bromocyclopentene (2.32 g, 15.8 mmol) in DMF (4 mL). The reaction was stirred over night. DCM (25 mL) was added and the mixture was filtered, the solids were washed with further DCM, water (30 mL) was added and the phases were separated. The aqueous phase was extracted with DCM (2×20 mL) and the combined organic phases were washed with H2O (20 mL), dried MgSO4, filtered and evaporated. The residue was purified by gradient silica gel chromatography (4-16% EtOAc in iso-hexane) which gave the title compound 1.24 g (30%). GC-MS EI m/z 213 (w), 196 (w), 152, 88, 57, 41.

Provenance & Evidence