Cesium carbonate → (2R,4S,4aS)-rel-11-fluoro-2,4-dimethyl-8-phenyl-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

HRID 578010Notes

Reaction equation

C([O-])([O-])=O.[Cs+].[Cs+].F[C:8]1[C:25]([F:26])=[C:24]2[C:11]([CH2:12][C:13]3([C@H:22]4[C@H:30]([CH3:31])[O:29][C@H:28]([CH3:32])[CH2:27][N:23]42)[C:18](=[O:19])[NH:17][C:16](=[O:20])[NH:15][C:14]3=[O:21])=[CH:10][C:9]=1/[C:33](=[N:40]/[OH:41])/[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>CN(C=O)C>[F:26][C:25]1[C:8]2[O:41][N:40]=[C:33]([C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)[C:9]=2[CH:10]=[C:11]2[C:24]=1[N:23]1[CH2:27][C@@H:28]([CH3:32])[O:29][C@@H:30]([CH3:31])[C@@H:22]1[C:13]1([C:14](=[O:21])[NH:15][C:16](=[O:20])[NH:17][C:18]1=[O:19])[CH2:12]2

Participants

Conditions

Temperature: 100 °C

Procedure

Cs2CO3 (130 mg, 0.0004 mmol) was added to a solution of (2R,4S,4aS)-rel-9,10-difluoro-8-[(E)-(hydroxyimino)(phenyl)methyl]-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 29, 100 mg, 0.0002 mmol) in DMF (1.5 mL), and the mixture was heated to 100° C. for 14 h. The reaction mixture was cooled to room temperature and filtered through a Celite bed. The solvent was removed, and the residue was subjected to reverse phase prep-HPLC purification (10 mM ammonium acetate in water, CH3CN) providing the title compound as a racemic mixture. Yield: 9.97 g (9%).

Workup

temperatureThe reaction mixture was cooled to room temperature
filtrationfiltered through a Celite bed
customThe solvent was removed
customphase prep-HPLC purification (10 mM ammonium acetate in water, CH3CN)

Sources & evidence

ORD record: ord-6551b645a1af4475abb0cc2b2375da89
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040528B2

Reaction notes

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