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

HRID 931622Notes

Reaction equation

HRID 931622 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-56153dc96bfc4d148ce6646280b27bf1
Source dataset
uspto-grants-2016_03
Patent number
US09296759B2

Reaction notes

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