(2'R,4'S,4'aS)-9',10'-difluoro-8'-[(E)-N-hydroxy-C-methylcarbonimidoyl]-2',4'-dimethylspiro[1,3-diazinane-5,5'-2,4,4a,6-tetrahydro-1H-[1,4]oxazino[4,3-a]quinoline]-2,4,6-trione → (2R,4S,4aS)-rel-11-fluoro-2,4,8-trimethyl-1,2,4,4a-tetrahydro-2'H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5'-pyrimidine]-2',4',6'(1'H,3'H)-trione

Participants

Reaction Conditions

Reaction Steps

To a solution of (2R,4S,4aS)-rel-9,10-difluoro-8-[(1E)-N-hydroxyethanimidoyl]-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[1,4-oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione (Intermediate 16, 250 mg, 0.63 mmol) in DMSO, was added K—O-t-Bu (47 mg, 0.636 mmol) and the mixture was heated to 120° C. for 12 hours. After cooling to room temperature and removal of solvent, the residue was purified using normal phase HPLC (95:5: Hexane:IPA) to give the title compound as a racemic mixture in the form of a pale yellow solid. Yield: 50 mg (20%).

Provenance & Evidence