Ammonia → (S)-2'-bromo-4'-fluoro-7'-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine

HRID 455654Notes

Reaction equation

[Br:1][C:2]1[CH:15]=[C:14]([F:16])[C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([O:17][CH3:18])=[CH:9][CH:10]=3)[C@@:5]3([CH2:23][O:22][CH2:21][C:20](=S)[NH:19]3)[C:4]=2[CH:3]=1.[NH3:25]>O1CCOCC1.[Hg](Cl)Cl>[Br:1][C:2]1[CH:15]=[C:14]([F:16])[C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([O:17][CH3:18])=[CH:9][CH:10]=3)[C@:5]3([N:19]=[C:20]([NH2:25])[CH2:21][O:22][CH2:23]3)[C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 55 °C

Procedure

In a 150-mL resealable vessel, the crude (S)-2′-bromo-4′-fluoro-7′-methoxyspiro[morpholine-3,9′-xanthene]-5-thione (1.0 g, 2.437 mmol) was dissolved in a dioxane solution of ammonia (0.5 M, 58.5 mL, 29.2 mmol). Mercury (II) chloride (0.993 g, 3.66 mmol) was added, and the vessel was sealed and heated in a 55° C. oil bath overnight. The mixture was then cooled and concentrated. The residue was filtered through Celite, rinsing with 10% MeOH-DCM (400 mL). The filtrate was concentrated, and the residue was purified through silica gel (150 mL) using 7.5% MeOH-DCM to afford 131 mg of (S)-2′-bromo-4′-fluoro-7′-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine

Workup

customthe vessel was sealed
temperatureThe mixture was then cooled
concentrationconcentrated
filtrationThe residue was filtered through Celite
washrinsing with 10% MeOH-DCM (400 mL)
concentrationThe filtrate was concentrated
customthe residue was purified through silica gel (150 mL)

Sources & evidence

ORD record: ord-9271195089ec43e6b4a2898e3287a6d3
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08497264B2

Reaction notes

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