Benzyl chloroformate → HCID 22464086, compound

HRID 1935621Notes

Reaction equation

HRID 1935621 reaction equation
O=C1C2C(=CC=CC=2)[C:4](=[O:11])[N:3]1[C:12]1[CH:17]=[CH:16][C:15]([N:18]2[C:26](=[O:27])C3C(=CC=CC=3)C2=O)=[CH:14][C:13]=1[O:29][CH2:30][C:31](=O)[CH3:32].[OH2:34].NN.[BH4-].[Na+].[C:39]([O-:42])(O)=O.[Na+].ClC(O[CH2:48][C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)=O>C1COCC1.CO>[CH2:39]([O:42][C:26]([NH:18][C:15]1[CH:16]=[CH:17][C:12]2[N:3]([C:4]([O:11][CH2:48][C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)=[O:34])[CH:31]([CH3:32])[CH2:30][O:29][C:13]=2[CH:14]=1)=[O:27])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

8

Reactant 5

HCID 10387Benzyl chloroformateHCID 24654Hydrazine hydrate (1:1)HCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 22464039HCID 22464039, compound

Product 1

HCID 22464086HCID 22464086, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

2-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-(2-oxopropoxy)phenyl]-1H-isoindole-1,3(2H)-dione (2.0 g, 4.5 mmol) is stirred as a suspension in dry THF. Hydrazine monohydrate (15 mL, 0.31 mol) is added and the mixture heated at reflux for 2 hours. The THF (top layer) is decanted and retained. The remaining mixture is extracted with CH2Cl2 (2×50 mL) and the organics combined. The THF/CH2Cl2 solution is dried (Na2SO4), filtered and solvent evaporated. The residue is chromatographed on silica gel using 0-2% MeOH/CH2Cl2 eluant to obtain a yellow solid. The solid is dissolved in MeOH (20 mL) and Sodium Borohydride (0.22 g, 5.7 mmol) added at 0° C. The mixture is allowed to warm to room temperature and stirred 5 hours. Solvent is evaporated to obtain a purple solid. This material is added to dry THF (30 mL) and NaHCO3 (0.46 g, 5.3 mmol) added. Benzyl chloroformate (0.76 mL, 5.3 mmol) is added dropwise and the mixture allowed to warm to room temperature while stirring overnight. The mixture is partitioned between water and EtOAc. The organic layer is washed with water then brine and dried (Na2SO4). Solvent is evaporated and the residue chromatographed on silica gel using 25% EtOAc/Heptane eluant. The oily product is triturated with heptane to give an off-white solid (51%); mp104-106° C. MS (EI) m/z 432 (M+), Anal. Calcd for C25H24N2O5: C, 69.43; H, 5.59; N, 6.48. Found: C, 69.21; H, 5.74; N, 6.49.

Workup

  1. temperaturethe mixture heated
  2. temperatureat reflux for 2 hours
  3. customThe THF (top layer) is decanted
  4. extractionThe remaining mixture is extracted with CH2Cl2 (2×50 mL)
  5. dry with materialThe THF/CH2Cl2 solution is dried (Na2SO4)
  6. filtrationfiltered
  7. customsolvent evaporated
  8. customThe residue is chromatographed on silica gel using 0-2% MeOH/CH2Cl2 eluant
  9. customto obtain a yellow solid
  10. customSolvent is evaporated
  11. customto obtain a purple solid
  12. additionadded
  13. temperatureto warm to room temperature
  14. stirringwhile stirring overnight
  15. customThe mixture is partitioned between water and EtOAc
  16. washThe organic layer is washed with water
  17. dry with materialbrine and dried (Na2SO4)
  18. customSolvent is evaporated
  19. customthe residue chromatographed on silica gel using 25% EtOAc/Heptane eluant
  20. customThe oily product is triturated with heptane

Sources & evidence

ORD record
ord-610ac29f541548f793d6eff6d6fbda84
Source dataset
uspto-grants-2002_05
Patent number
US06387896B1

Reaction notes

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