Potassium Carbonate → 8-Bromo-2-ethynyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene

HRID 1848973Notes

Reaction equation

HRID 1848973 reaction equation
[Br:1][C:2]1[CH:17]=[CH:16][C:5]2[C:6]3[N:7]=[C:8]([CH:14]=O)[S:9][C:10]=3[CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1.[N+](=[C:20](P(OC)(OC)=O)C(OC)=O)=[N-].C(=O)([O-])[O-].[K+].[K+]>CO>[Br:1][C:2]1[CH:17]=[CH:16][C:5]2[C:6]3[N:7]=[C:8]([C:14]#[CH:20])[S:9][C:10]=3[CH2:11][CH2:12][O:13][C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 582041688-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carbaldehydeHCID 714010502-Diazonio-2-(dimethoxyphosphoryl)-1-methoxyethen-1-olate

Product 1

HCID 582040918-Bromo-2-ethynyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azuleneYield 38.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

8-Bromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carbaldehyde (0.688 g, 2.2 mmol) was dissolved in methanol (8 mL) and methyl 2-diazo-2-(dimethoxyphosphoryl)acetate (0.923 g, 4.44 mmol) was added followed by potassium carbonate (0.613 g, 4.44 mmol). The resulting mixture was stirred 12 h at ambient temperature and quenched by the addition of sat. NH4Cl aqueous solution and stirred 5 min. Diluted with H2O and EtOAc, extracted the aqueous layer with EtOAc (2×) and the combined organic portions were washed with brine. Dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by ISCO chromatography (24 g column, 0-25% EtOAc/heptane) to provide 8-Bromo-2-ethynyl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene as an oil (0.26 g, 38% yield). 1H NMR (400 MHz, CDCl3) δ 8.35 (d, J=8.5, 1H), 7.31-7.18 (m, 2H), 4.37 (t, J=5.1, 2H), 3.49 (s, 1H), 3.33 (t, J=5.1, 2H)

Workup

  1. customquenched by the addition of sat. NH4Cl aqueous solution
  2. stirringstirred 5 min
  3. additionDiluted with H2O and EtOAc
  4. extractionextracted the aqueous layer with EtOAc (2×)
  5. washthe combined organic portions were washed with brine
  6. dry with materialDried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by ISCO chromatography (24 g column, 0-25% EtOAc/heptane)

Sources & evidence

ORD record
ord-bf8741f63e72464bb9d232c52e41390a
Source dataset
uspto-grants-2015_02
Patent number
US08952043B2

Reaction notes

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