Ammonia → (5)-Tert-butyl 2'-bromo-7'-iodo-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthene]-5-ylcarbamate

HRID 455628Notes

Reaction equation

HRID 455628 reaction equation
[Br:1][C:2]1[CH:15]=[CH:14][C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([I:16])=[CH:9][CH:10]=3)[C@:5]3([CH2:21][O:20][CH2:19][C:18](=S)[NH:17]3)[C:4]=2[CH:3]=1.N.[CH3:24][C:25]([O:28][C:29]([O:31]C(OC(C)(C)C)=O)=O)([CH3:27])[CH3:26].CC[N:41](CC)CC>O1CCOCC1.[Hg](Cl)Cl.C(Cl)Cl>[Br:1][C:2]1[CH:15]=[CH:14][C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([I:16])=[CH:9][CH:10]=3)[C@@:5]3([N:17]=[C:18]([NH:41][C:29](=[O:31])[O:28][C:25]([CH3:27])([CH3:26])[CH3:24])[CH2:19][O:20][CH2:21]3)[C:4]=2[CH:3]=1

Participants

8

Reactant 4

HCID 222AmmoniaHCID 8471TriethylamineHCID 90495Di-tert-butyl dicarbonateHCID 86658380(S)-2'-bromo-7'-iodospiro[morpholine-3,9'-xanthene]-5-thione

Product 1

HCID 67436611(5)-Tert-butyl 2'-bromo-7'-iodo-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthene]-5-ylcarbamate

Reagents, catalysts & solvents 3

HCID 24085Mercuric ChlorideCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

In a 350-mL resealable vessel, the (S)-2′-bromo-7′-iodospiro[morpholine-3,9′-xanthene]-5-thione (1.25 g, 2.56 mmol) was dissolved in a dioxane solution of ammonia (0.5 M, 61.5 mL, 30.7 mmol). After the solid had dissolved, mercury(II) chloride (1.043 g, 3.84 mmol) was added. The vessel was sealed and placed in a 55° C. oil bath overnight. The reaction was filtered through Celite, rinsing with DCM (50 mL). The mixture was concentrated to remove the DCM, and Boc2O (0.84 g, 3.84 mmol) and Et3N (0.535 mL, 3.84 mmol) were added. After 1.5 h, the mixture was concentrated, and the residue was purified by chromatography (15% EtOAc/hexanes) to afford impure (S)-tert-butyl 2′-bromo-7′-iodo-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-5-ylcarbamate.

Workup

  1. dissolutionAfter the solid had dissolved
  2. customThe vessel was sealed
  3. customplaced in a 55° C.
  4. customovernight
  5. filtrationThe reaction was filtered through Celite
  6. washrinsing with DCM (50 mL)
  7. concentrationThe mixture was concentrated
  8. additionwere added
  9. concentrationthe mixture was concentrated
  10. customthe residue was purified by chromatography (15% EtOAc/hexanes)

Sources & evidence

ORD record
ord-304c9c9134324e989b35c4df17c9d291
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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