反应详情

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).

1. stirringStirring
2. waitwas continued for an additional 0.5 h
3. customthe two layers were separated
4. washThe organic solution was washed with sat. NaHCO3, 1N HCl, sat. NaHCO3, and brine
5. concentrationconcentrated under reduced pressure
6. stirringThe solution was stirred at room temperature for 18 h
7. filtrationfiltered over a pad of celite
8. concentrationThe resulting solution was concentrated
9. customto afford an off white residue
10. washwashed with sat. Na2CO3
11. customThe layers were separated
12. extractionthe aqueous layer was extracted three times with CH2Cl2
13. concentrationconcentrated