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

Temperature

40 °C

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).

1. concentrationThe reaction mixture was concentrated under reduced pressure, diethyl ether
2. additionwas added to the residue
3. extractionthe mixture was extracted with water
4. extractionthe mixture was extracted with ethyl acetate
5. washThe extract was washed with brine
6. dry with materialdried over anhydrous sodium sulfate
7. customThe solvent was evaporated under reduced pressure
8. additionTo a solution of the residue in ethyl acetate (5 mL) was added 4 N hydrogen chloride-ethyl acetate solution (22 mL)
9. stirringthe mixture was stirred at room temperature for 2 hr
10. concentrationThe reaction mixture was concentrated under reduced pressure, acetonitrile
11. additionwas added to the residue
12. filtrationthe precipitate was collected by filtration
13. dissolutionThe obtained solid was dissolved in 10% aqueous acetonitrile (17 mL)
14. filtrationan insoluble material was filtered off
15. additionTo the mother liquor was added acetonitrile (50 ml)
16. stirringthe mixture was stirred overnight
17. filtrationThe obtained crystals were collected by filtration

ORD record

ord-b5071c5e8c5c400dbc18e916ee01fd3d

Source dataset

uspto-grants-2014_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08722662B2