反应详情

To a stirred mixture of 3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]-propionic acid (2.8 g, 7.6 mmol) and N,N-diisopropylethylamine (2.6 mL, 15 mmol) in DMF (31 mL) was added 2-chloro-1-methylpyridinium iodide (3.9 g, 15 mmol). Once the solids had dissolved, (3-methylaminopropyl)carbamic acid 9H-fluoren-9-ylmethyl ester hydrochloride salt (2.63 g, 7.58 mmol) was added and the resulting mixture was stirred at room temperature until essentially complete by HPLC and LCMS. The mixture was then concentrated under reduced pressure to remove most of the DMF and the residue was dissolved in DCM (30 mL). This mixture was washed with water (3×20 mL) and brine (3×20 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (0-20% MeOH in DCM) to give the title compound (5.0 g, 97% yield) as a white solid.

1. dissolutionOnce the solids had dissolved
2. concentrationThe mixture was then concentrated under reduced pressure
3. customto remove most of the DMF
4. dissolutionthe residue was dissolved in DCM (30 mL)
5. washThis mixture was washed with water (3×20 mL) and brine (3×20 mL)
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by silica gel flash chromatography (0-20% MeOH in DCM)