Hydrochloric Acid → Ethyl (3S)-3-hydroxy-3-(6-((methylamino)carbonyl))-2-naphthyl)-3-(1-trityl-1H-imidazil-4-yl) propanoate

Participants

Reaction Steps

150 mL of ethanol and 6.9 mL (23.5 mmol, 3 eq) of titanium tetraisopropoxide were added to 5 g (7.84 mmol) of tert-butyl (3S)-3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate. The mixture was stirred at 60˜65° C. for 28 hours and 40 minutes. 50 mL of 1N hydrochloric acid was added to at 0˜10° C., followed by dilution with 150 mL of ethyl acetate. 50 mL of an aqueous saturated sodium chloride solution was added, and the layers were separated. The organic layer was washed successively with a mixed solution of 25 mL of 1N hydrochloric acid and 65 mL of an aqueous saturated sodium chloride solution two times, 25 mL of an aqueous saturated sodium bicarbonate solution, and 50 mL of an aqueous saturated sodium chloride solution two times. After concentrated under reduced pressure, 50 mL of ethyl acetate, 10 mL of THF and 10 mL of water were added to the concentration residue and the layers were separated. The organic layer was washed with 10 mL of an aqueous saturated sodium chloride solution two times. After concentrated under reduced pressure, 15 mL of IPE was added to the concentrated residue, crystals were loosened, filtered, and washed with 5 mL of IPE two times. Vacuum drying (40° C.) to a constant weight afforded 3.8 g of ethyl (3S)-3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate (yield 80%, enantiomer excess 94.8% ee).

Provenance & Evidence