Triethylamine → (+/-)-N-tert-Butoxycarbonyl-N-benzylglycyl-phenylalanine Methyl Ester

Participants

Reaction Steps

To a stirring suspension of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (1.15 g, 6 mmol) in reagent grade CH2Cl2 (20 mL) was added a solution of pentafluorophenol (1.5 g, 8.1 mmol) in CH2Cl2 (10 mL) followed by a solution of N-Boc-N-Benzyl glycine 3 [Naylor 1993] (1.32 g, 5.0 mmol) in CH2Cl2 (20 mL). The solution was stirred at ambient temperature for 1 h then triethylamine (2.5 mL, 18 mmol) was added with additional CH2Cl2 (10 mL). The (±)-phenylalanine methyl ester hydrochloride (1.32 g, 5 mmol) was then added in small portions. The final solution was stirred for 20 h at ambient temperature and then was washed with aqueous sodium carbonate (1 M, 100 mL), aqueous citric acid (1 M, 100 mL) and water (50 mL). The organic phase was dried (K2CO3) and concentrated to afford the crude product. Column chromatography of the crude material (silica gel, EtOAc:hexanes, gradient 1:3 3:2) to provided 5 as a clear viscous oil (2.17 g, 102%, solvent heavy). 1H NMR (400 MHz, CDCl3): δ 1.45 (s, 9H), 2.99-3.16 (bm, 2H), 3.72 (s, 3H), 3.79 (bd, J=16.1 Hz, overlapped with bm, 2H), 4.30-4.50 (bm, 2H), 4.85 (m, 1H), 6.27 (bs, 0.3H), 6.63 (bs, 0.3H), 7.05-7.11 (bm, 2H), 7.17-7.34 (m, 8H); 13C NMR (100 MHz, CDCl3): δ 28.2, 37.8, 50.2, 51.2 (v. broad), 52.3, 52.8 (broad), 81.1, 127.1, 127.6, 128.1 (broad), 128.6, 129.1, 135.6, 136.9, 155.3 (broad), 168.9 (broad), 171.5.

Provenance & Evidence