Dimethylformamide → Benzhydrylidene Aza-phenylpropargylglycinyl-D-phenylalanine tert-butyl ester

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Reaction Steps

A solution of benzhydrylidene aza-propargylglycinyl-D-phenylalaninyl tert-butyl ester (1, 500 mg, 1.04 mmol) in 10 mL of a 1:1 (v/v) DMF:Et2NH mixture was treated with Pd(PPh3)2Cl2 (73 mg, 0.104 mmol), CuI (40 mg, 0.208 mmol), and iodobenzene (0.15 mL, 1.35 mmol) under inert atmosphere. The solution was stirred for 12 h, diluted with 40 mL of EtOAc, and washed with saturated NaHCO3 (3×50 mL). After drying over Na2SO4, the solution was filtered, and concentrated under reduced pressure to a residue, which was purified by silica gel chromatography using 30% Et2O in petroleum ether to give aza-dipeptide 18a as orange foam (504 mg, 87%): Rf 0.41 (6:4 petroleum ether:Et2O); [α]D20 −24.1 (c 1.06, CHCl3); 1H NMR (400 MHz, CDCl3) δ 1.47 (9H, s), 3.30-3.21 (2H, m), 4.20 (1H, d, J=18.0 Hz), 4.54 (1H, d, J=17.9), 4.88-4.82 (1H, m), 7.59-7.20 (20H, m). 13C NMR (100 MHz, CDCl3) δ 171.3, 158.2, 157.7, 139.3, 137.0, 136.2, 132.0, 130.4, 130.2, 130.1, 129.8, 129.1, 129.0, 128.8, 128.7, 128.6, 127.3, 123.4, 84.8, 84.5, 82.3, 55.5, 38.9, 36.4, 28.5. HRMS m/z 558.2769, (M+H)+ calcd for [C36H36N3O3]+: 558.2751. IR (neat) 1731, 1679, 1488, 1366, 1150, 756, 691.

Provenance & Evidence