Chlorotrimethylsilane → HCID 66996988, compound

Participants

Reaction Conditions

Reaction Steps

To 0.39 g (6.0 mmol) of Zn powder under Ar2 is added 0.5 mL of DMF and then 26 μL (0.3 mmol) of 1,2-dibromoethane. After stirring at 60° C. for 30 minutes, the mixture is cooled and 7.6 μL (0.06 mmol) of TMSCl is added. After stirring for 30 minutes, 0.34 g (1.0 mmol) of 4-iodo-2-tert-butoxycarbonylamino-butyric acid methyl ester is added and the mixture is stirred at 35° C. for 30 minutes. The mixture is cooled to rt, and 23 mg (0.040 mmol) of Pd(dba)2, 24 mg (0.080 mmol) of (o-tolyl)3P, and then 0.22 mg (0.95 mmol) 3-iodobenzonitrile are added. After stirring at rt for 3 h, EtOAc is added and the mixture is washed with saturated NH4Cl and brine. The extract is concentrated and purified by preparative HPLC to provide 0.14 g (44%) of Boc-(3-cyano)homophenylalanine-OMe. To 0.12 g (0.38 mmol) of this material in 1 mL of 1:1 MeOH/THF is added 0.38 mL (0.75 mmol) of 2 M NaOH. After stirring for 1 h, 1 M NaHSO4 is added, and the mixture is extracted with EtOAc. The extract is washed with brine, dried over Na2SO4, filtered, and concentrated to provide 0.11 g (96%) of 2-[(tert-butoxycarbonyl)amino]-4-(3-cyanophenyl)butanoic acid.

Provenance & Evidence