1,2-Dichloroethane → 1,1-Dimethylethyl (1S,4S)-5-(3-methyl-L-valyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate

Participants

Reaction Steps

To a solution of 1,1-dimethylethyl (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (11.25 g, 57.6 mmol) in CH2Cl2 (567 mL) was added EDC (40.8 g, 213 mmol), HOBt (10.86 g, 70.9 mmol), 3-methyl-N-{[(phenylmethyl)oxy]carbonyl}-L-valine (18.82 g, 70.9 mmol), and NMM (37.4 g, 340 mmol). The reaction mixture was stirred at room temperature for 18 h. The reaction was diluted with water (75 ml) and sat. Na2CO3 (75 ml). Stirring was continued for an additional 0.5 h then the two layers were separated. The organic solution was washed with sat. NaHCO3, 1N HCl, sat. NaHCO3, and brine. The organic layer was passed over a phase separator and concentrated under reduced pressure. To the residue was added ethanol (567 ml), 10% Pd/C (6.04 g) and ammonium formate (35.8 g, 567 mmol). The solution was stirred at room temperature for 18 h and then filtered over a pad of celite. The resulting solution was concentrated to afford an off white residue. The residue was dissolved in CH2Cl2 and washed with sat. Na2CO3. The layers were separated and the aqueous layer was extracted three times with CH2Cl2. The combined CH2Cl2 extracts were passed over a phase separator and concentrated to afford the desired product (17.1 g, 54.9 mmol) as an off white residue. LCMS (m/z): 312.2 (M+H).

Provenance & Evidence