Triethylamine → (benzyloxycarbonyl)difluoromethyl 5-(Cbz-amino)-4-oxopentanoate

Triethylamine (3.5 mL; 2.5 g; 25 mmol) was added using a syringe to a stirred mixture of the crude product of 3a (8.6 g; 20 mmol) and 5-(Cbz-amino)-4-oxopentanoic acid (6.63 g; 25 mmol) in dry acetonitrile (100 mL). The mixture was refluxed for 18 h, then the solvent was evaporated and the dark red residue was dissolved in diethyl ether (100 mL) and 0.5 M HCl (100 mL). After mixing thoroughly, the ether layer was washed with water (2×15 mL), saturated NaHCO3 (2×15 mL), and saturated NaCl solution (1×15 mL), then dried (MgSO4). After filtration and evaporation, the residue was purified by flash chromatography on a 60×55 mm silica gel 60 column eluted with dichloromethane-diethyl ether (9:1) (1000 mL), collecting 10×75 mL fractions. After evaporation of fractions 2-5 and vacuum-drying (0.02 mm Hg), 6.7 g (74%) product was obtained (red-orange solid mp 48-50° C.).

1. temperatureThe mixture was refluxed for 18 h
2. customthe solvent was evaporated
3. dissolutionthe dark red residue was dissolved in diethyl ether (100 mL)
4. additionAfter mixing thoroughly
5. washthe ether layer was washed with water (2×15 mL), saturated NaHCO3 (2×15 mL), and saturated NaCl solution (1×15 mL)
6. dry with materialdried (MgSO4)
7. filtrationAfter filtration and evaporation
8. customthe residue was purified by flash chromatography on a 60×55 mm silica gel 60 column
9. washeluted with dichloromethane-diethyl ether (9:1) (1000 mL)
10. customcollecting 10×75 mL fractions
11. customAfter evaporation of fractions 2-5
12. customvacuum-drying (0.02 mm Hg)

ORD record

ord-9d6c8f66bb1646b7a41dcab69084fc3e

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09249086B2