Iodine → (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(4-cyano-2,6-dimethylphenyl)propanoate

Participants

Reaction Conditions

Reaction Steps

A 50 mL three-necked round bottom flask equipped with an addition funnel, magnetic stirrer, heating mantel, and thermocouple was charged under nitrogen dry DMAc (2 mL), I2 (38.1 mg, 0.15 mmol) and zinc powder activated (washed with 10% HCl, rinsed with H2O and acetone) (393 mg, 6 mmol). The resulting mixture was stirred at 23° C. until the red color of I2 disappeared (2 minutes). A solution of Boc-β-iodo-L-alanine methyl ester (1 g, 3 mmol) in DMAc (2 mL) was added slowly, (temperature change from 21° C. to 29° C.) and the resulting mixture was stirred at 80° C. for 0.5-1 hour, then co cooled to 35° C. To the resulting mixture were added, successively, 4-bromo-3,5-dimethyl-benzonitrile (315 mg, 1.5 mmol) in DMAc (6 mL), P(o-tol)3 (36.5 mg, 0.12 mmol) and Pd2(dba)3 (55 mg, 0.06 mmol). The resulting mixture was heated to 70° C., with stirring for 1 hour, then cooled to ambient temperature. The resulting mixture was diluted with EtOAc (15 mL) and filtered with STAND SUPER-CEL 815520. The EtOAc solution was quenched with 1 N HCl (40 mL) and extracted with ethyl acetate (20 mL). The combined organic phases were washed with H2O (2×50 mL) and then with 50% brine, dried over Na2SO4, filtered and evaporated to dryness in vacuo to yield a brown solid. The title compound was crystallized from EtOAc (5 mL) and heptane (40 mL) to yield a white solid.

Provenance & Evidence