Dicyclohexylcarbodiimide → Boc-norvaline leucinamide

Participants

Reaction Conditions

Reaction Steps

Boc-norvaline (2.0 g, 9.2 mmol) and leucinamide (1.53 g, 9.2 mmol) were dissolved in dry DMF (90 mL). The reaction was cooled to 0° C. and DCC (2.3 g, 11 mmol), HOBt (1.48 g, 11 mmol), and DEA (1.9 mL, 11 mmol) added. The mixture was stirred for 20 min at 0° C. and allowed to slowly warm to room temperature overnight (17 h). The mixture was concentrated to 1/3 its original volume, cooled, and filtered. The filtrate was concentrated, affording a yellow oil which was purified by column chromatography (SiO2, 1:1 hexanes/EtOAc→EtOAc) providing Boc-norvaline-leucinamide as white solid (selected signals 400 MHz, 1H NMR, CDCI3: δ 4.93 (m, 1 H), 4.45 (m, 1 H), 3.99 (m, 1 H), 1.81-1.71 (m, 2 H), 1.68-1.50 (m, 4 H), 1.41 (s, 9 H), 1.4-1.3 (m, 2 H), 0.9 (m, 9 H)). The Boc-protecting group was removed by treatment of Boc-norvaline-leucinamide (1.5 g, 4.6 mmol) with 50% TFA/DCM (60 mL) at room temperature (30 min). The reaction mixture was concentrated in vacuo and the peptide triturated with diethyl ether and dried in vacuo overnight providing norvaline-leucinamide as a foamy white solid (Electrospray MS M+H=230.1). Boc-valine (233 mg, 1.1 mmol) and norvaline-leucinamide (246 mg, 1.1 mmol) were dissolved in DMF (5 mL) and the solution cooled to 0° C. DCC (266 mg, 1.3 mmol), HOBt (174 mg, 1.3 mmol), and DIEA (224 μL, 1.3 mmol) were added and the reaction allowed to slowly warm to RT (overnight, 17 h). The reaction was filtered and the filtrate concentrated in vacuo affording a solid which was purified by column chromatography (SiO2, EtOAc). This provided the desired Boc-valine-norvaline-leucinamide as a white solid.

Provenance & Evidence