1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 57635360, compound

HRID 1971086Notes

Reaction equation

HRID 1971086 reaction equation
[C:1]([NH:4][NH:5][C:6](=[O:37])[C@@H:7]([NH:12][C:13]([C:15]1[N:16]=[C:17]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[N:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][C:19]=12)=[O:14])[C:8]([CH3:11])([CH3:10])[CH3:9])(=O)[CH3:2].C1CCN2C(=NCCC2)CC1.CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC>C1COCC1>[CH3:10][C:8]([CH3:9])([CH3:11])[C@H:7]([NH:12][C:13]([C:15]1[N:16]=[C:17]([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[N:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:28])[CH3:29])=[O:25])[CH2:20][C:19]=12)=[O:14])[C:6]1[O:37][C:1]([CH3:2])=[N:4][N:5]=1

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 2724994Methyl N-(triethylammoniosulfonyl)carbamate2×HCID 57635603HCID 57635603, compound

Product 1

HCID 57635360HCID 57635360, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
150 °C

Procedure

The intermediate 14D (48 mg, 94 μmol) was taken up in THF (1 mL) and added to a 2 mL microwave reaction vial. DBU (21 μL, 0.14 mmol) was added to the reaction, followed by the Burgess reagent (112 mg, 468 μmol). The vial was capped and the reaction mixture was heated to 150° C. for 5 minutes, after which some starting material still remained. Additional Burgess reagent (1 equiv) was added and the reaction was heated to 150° C. for 10 minutes. LC/MS showed that the starting material was consumed. The reaction was diluted with of saturated aqueous NaHCO3 (1 mL) and EtOAc (2 mL). The organic layer was removed and the aqueous layer extracted with EtOAc (2 mL). The organic layers were combined, dried with anhydrous Na2SO4, filtered and evaporated. The residue was purified by Flash chromatography on silica using a gradient from 10% EtOAc/Hexanes to 60% EtOAc/Hexanes. This provided intermediate 14E as a clear oil (25 mg, 54% yield). LCMS (+ESI) m/z 495.3 [M+H]+.

Workup

  1. additionadded to a 2 mL microwave reaction vial
  2. customThe vial was capped
  3. temperaturethe reaction was heated to 150° C. for 10 minutes
  4. customwas consumed
  5. additionThe reaction was diluted with of saturated aqueous NaHCO3 (1 mL) and EtOAc (2 mL)
  6. customThe organic layer was removed
  7. extractionthe aqueous layer extracted with EtOAc (2 mL)
  8. dry with materialdried with anhydrous Na2SO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified by Flash chromatography on silica using a gradient from 10% EtOAc/Hexanes to 60% EtOAc/Hexanes

Sources & evidence

ORD record
ord-9d89300592be4ecf8191a59e5f52ae09
Source dataset
uspto-grants-2013_04
Patent number
US08431565B2

Reaction notes

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