Ethylmorpholine → Boc-Ala-Phe-OMe

Participants

Reaction Conditions

Reaction Steps

To a solution of Boc-Ala-OH (0.50 g, 2.64 mmol) and N-ethyl morpholine (0.336 mL, 2.64 mmol) in THF (10 mL) at −18° C. was added i-butyl chloroformate (0.317 mL, 2.44 mmol). After an activation period of 10 min a solution of Phe-OMe (0.406 g, 1.88 mmol) and N-ethyl morpoholine (0.240 mL, 1.88 mmol) in DMF (4 mL) was added dropwise. The reaction mixture was stirred under nitrogen at −18° C. for 1 h then overnight at room temperature. The reaction mixture was cooled to 0° C. followed by addition of NaHCO3 (10 mL, 5% aqueous solution). After 10 min this solution was warmed to room temperature and diluted with EtOAc (5 mL). The aqueous layer was removed and washed 2 with 20 mL EtOAc. The organics were combined and washed 3 with 10 mL 1 N HCl, dried over Na2SO4 and concentrated. The residue was purified by flash column chromatography (70% EtOAc/haxanes) to the product as a white solid (0.159 g, 91%). 1H NMR (CDCl3) 7.31 (m, 3H), 7.14 (m, 2H), 6.63 (d, J=7.4 Hz, 1H), 5.05 (br s, 1H), 4.87 (q, J=6.9 Hz, 1H), 4.18 (br s, 1H), 3.73 (s, 3H), 3.18 (dd, J=13.9, 6.1 Hz, 1H), 3.10 (dd, J=13.9, 5.8 Hz, 1H), 1.46 (s, 9H), 1.33 (d, J=6.9 Hz, 3H); 13C NMR (CDCl3) 172.2, 171.7, 155.3, 135.7, 129.2, 128.5, 127.1, 80.0, 53.1, 52.3, 50.0, 37.8, 28.2, 18.2; IR (KBr) 3315, 2978, 1744, 1708, 1666, 1522, 1453, 1366,1168; HRMS calcd for C18H27N2O (M+H)+ 351.1920 found 351.1916.

Provenance & Evidence