Sodium Hydroxide → 1-{[(6S,7R)-7-(4-chloro-3-fluorophenyl)-1,4-oxazepan-6-yl]methyl}-2-oxo-1,2-dihydropyridine-3-carboxylic acid monohydrochloride

Participants

Reaction Conditions

Reaction Steps

2 N Aqueous sodium hydroxide solution (8.73 mL) was added to a solution of tert-butyl (6R,7R)-7-(4-chloro-3-fluorophenyl)-6-{[3-(methoxycarbonyl)-2-oxopyridin-1(2H)-yl]methyl}-1,4-oxazepane-4-carboxylate (2.88 g) in ethanol (25 mL), and the mixture was stirred at 40° C. for 2 hr. The reaction mixture was concentrated under reduced pressure, diethyl ether was added to the residue, and the mixture was extracted with water. The aqueous layer was neutralized with 1 N hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. To a solution of the residue in ethyl acetate (5 mL) was added 4 N hydrogen chloride-ethyl acetate solution (22 mL), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure, acetonitrile was added to the residue, and the precipitate was collected by filtration. The obtained solid was dissolved in 10% aqueous acetonitrile (17 mL), and an insoluble material was filtered off. To the mother liquor was added acetonitrile (50 ml), and the mixture was stirred overnight. The obtained crystals were collected by filtration to give the title compound (2.01 g).

Provenance & Evidence