Hydrochloric Acid → 6-((7S)-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methyl-2-naphthamide

Participants

Reaction Conditions

Reaction Steps

7 mL of THF and 0.42 mL (2.47 mmol, 4 eq) of diisopropylethylamine were added to 0.35 g (0.62 mmol) of 6-[(1S)-1,3-dihydroxy-1-(1-trityl-1H-imidazol-4-yl)propyl]-N-methyl-2-naphthamide. 0.072 mL (0.93 mmol, 1.5 eq) of methylsulfonyl chloride was added dropwise at 0˜5° C., and the mixture was stirred at 0˜5° C. for 40 minutes. 1.8 mL of methanol and 3.5 mL of acetonitrile were added, and the mixture was stirred at 60˜65° C. for 4 hours. After cooled to 25° C., 7 mL of ethyl acetate was added, 3.5 mL of 0.5N hydrochloric acid-aqueous saturated ammonium chloride solution was added dropwise at 0˜5° C., and 1 mL of water was added. The aqueous layer was taken, and the organic layer was back extracted with 2 mL of 0.5N hydrochloric acid-aqueous saturated ammonium chloride solution two times. The aqueous layers were combined, and a pH was adjusted to 8 with a 1N aqueous sodium hydroxide solution. The material was stirred at 25° C. for 2 hours, and at 0˜5° C. for 2 hours. Crystals were filtered, and washed with water. Vacuum drying (50° C.) to a constant weight afforded 0.87 g of 6-[(7S)-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl]-N-methyl-2-naphthamide (yield 62%, enantiomer excess 98.2% ee).

Provenance & Evidence