1-(3,4-Dichlorophenyl)-3-azabicyclo[3.1.0]hexane-2,4-dione → HCID 57871306, compound

HRID 332132Notes

Reaction equation

HRID 332132 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]23[CH2:14][CH:13]2[C:12](=O)[NH:11][C:10]3=[O:16])[CH:5]=[CH:6][C:7]=1[Cl:8].COCCO[AlH2-]OCCOC.[Na+]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]23[CH2:14][CH:13]2[CH2:12][NH:11][C:10]3=[O:16])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

4

Reactant 2

HCID 127198261-(3,4-Dichlorophenyl)-3-azabicyclo[3.1.0]hexane-2,4-dioneHCID 16684438Red-Al

Product 1

HCID 57871306HCID 57871306, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

1-(3,4-dichlorophenyl)-3-aza-bicyclo[3.1.0]hexane-2,4-dione and toluene were combined in a 500 mL round-bottomed flask and stirred under Ar (g) for 10 min while cooling in an ice bath. Red-Al® was added via addition funnel drop-wise over several minutes. Upon complete addition, the ice bath was removed and the reaction stirred at ambient temperature overnight. The reaction mixture was cooled in an ice bath and 150 mL of 5N NaOH was carefully added. The phases were separated and the aqueous phase was extracted with toluene (2×100 mL), DCM (3×100 mL), and the organic layers combined. The organic layer was washed with brine (200 mL) and dried over sodium sulfate for 8 h. The mixture was filtered, concentrated in vacuo, and dried to afford 5 g of a dark brown semi-solid. The semi-solid was purified on a silica gel column eluting with 20% EtOAc in hexanes increasing the polarity to 30% EtOAc and finally 50% EtOAc. The desired fractions containing the product were combined, concentrated, and dried to afford a light yellow solid. Yield: 2.0 g 30%; LCMS (+) ESI: m/z=242 [M]+; m/z=264 [M+Na]+; 1H NMR (300 MHz, CDCl3) δ□ 7.52 (d, 1H, ArH), 7.39 (d, 1H, ArH), 7.28 (dd, 1H, ArH), 6.02 (bs, 1H, NH), 3.64 (dd, 1H, NHCH2), 3.40 (d, 1H, NHCH2), 2.28 (m, 1H, NHCH2CH), 1.50 (dd, 1H, ArCCH2), 1.26 (m, 1H, ArCCH2).

Workup

  1. temperaturewhile cooling in an ice bath
  2. additionUpon complete addition
  3. customthe ice bath was removed
  4. temperatureThe reaction mixture was cooled in an ice bath
  5. addition150 mL of 5N NaOH was carefully added
  6. customThe phases were separated
  7. extractionthe aqueous phase was extracted with toluene (2×100 mL), DCM (3×100 mL)
  8. washThe organic layer was washed with brine (200 mL)
  9. dry with materialdried over sodium sulfate for 8 h
  10. filtrationThe mixture was filtered
  11. concentrationconcentrated in vacuo
  12. customdried

Sources & evidence

ORD record
ord-fefafbb4f8034cbf931fd9b2b0ef5dc7
Source dataset
uspto-grants-2014_11
Patent number
US08877798B2

Reaction notes

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