Benzyl Alcohol → HCID 54563670, compound

HRID 1603033Notes

Reaction equation

HRID 1603033 reaction equation
[C:1]([O-:7])(=O)CC([O-])=O.O=S(Cl)Cl.[N-:12]=[N+]=[N-].[Na+].[CH2:16]([OH:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.N[C:25]1[CH:30]=[CH:29][C:28]([CH:31]([C:36]([O:38][CH3:39])=[O:37])[C:32]([O:34][CH3:35])=[O:33])=[C:27]([N+:40]([O-:42])=[O:41])[CH:26]=1>CN(C=O)C.ClCCCl.O.CC(C)=O.CCOC(C)=O>[CH2:16]([O:23][C:1]([C:25]1[CH:30]=[CH:29][C:28]([CH:31]([C:36]([O:38][CH3:39])=[O:37])[C:32]([O:34][CH3:35])=[O:33])=[C:27]([N+:40]([O-:42])=[O:41])[C:26]=1[NH2:12])=[O:7])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

11

Reactant 5

HCID 244Benzyl AlcoholHCID 9084Malonate IonHCID 24386Thionyl ChlorideHCID 33557Sodium AzideHCID 54082503HCID 54082503, compound

Product 1

HCID 54563670HCID 54563670, compoundYield 81%

Reagents, catalysts & solvents 5

HCID 6228DimethylformamideCatalystHCID 111,2-DichloroethaneSolventHCID 180AcetoneSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of the above malonate (3.44 g, 11.6 mmol), SOCl2 (1.0 mL, 13.9 mmol) and DMF (4 drops) in 1,2-dichloroethane (60 mL) was stirred under reflux for 1 h, cooled and evaporated. The residue was dissolved in Me2CO (30 mL) and added dropwise over 10 min to a vigorously stirred solution of sodium azide (2.26 g, 35 mmol) in water (30 mL) and acetone (100 ml) at 0° C. After a further 30 min at 0° C., EtOAc (100 mL) was added, most of the Me2CO was evaporated, and the EtOAc layer was washed with water, dried (Na2SO4), and evaporated. The residue was dissolved in dry toluene (35 mL) and stirred at reflux for 40 min. Benzyl alcohol (2.2 mL, 21 mmol) was added to the cooled solution and the mixture stirred at 20° C. for 2 h [until a sample spotted on a tlc plate no longer showed the formation of yellow dimethyl (4-amino-2-nitrophenyl)malonate]. The mixture was then evaporated and the residue was distilled in a Kugelrohr (1 mm Hg, 90° C.) to remove excess benzyl alcohol. Flash chromatography on silica gel, eluting with petroleum ether/EtOAc (3:1) gave dimethyl [4-(benzyloxycarbonyl)-amino-2-nitrophenyl]malonate as a yellow oil (3.77 g, 81%). 1H NMR (CDCl3) δ8.16 (d, J=2.3 Hz, 1H, H-3), 7.59 (dd, J=8.5, 2.3 Hz, 1H, H-5), 7.42-7.33 (m, 6H, H-6 and Ph), 7.11 (s, 1H, NH), 5.25 (s, 1H, ArCH), 5.22 (s, 2H, OCH2Ph), 3.78 (s, 6H, CO2Me); 13C NMR δ167.9, (CO2Me), 152.8 (NCO2), 149.0, 139.1, 135.4, 131.9, 128.7, 128.6, 128.4, 122.7, 121.9, 114.6 (aromatic C), 67.6 (OCH2Ph), 53.5 (ArCH), 53.2 (OMe); MS (DEI) m/z 402 (2%, M+), 91 (100%, C7H7); HRMS calcd. for C19H18N2O8 402.10631, found 402.10594.

Workup

  1. temperatureunder reflux for 1 h
  2. temperaturecooled
  3. customevaporated
  4. dissolutionThe residue was dissolved in Me2CO (30 mL)
  5. customwas evaporated
  6. washthe EtOAc layer was washed with water
  7. dry with materialdried (Na2SO4)
  8. customevaporated
  9. dissolutionThe residue was dissolved in dry toluene (35 mL)
  10. temperatureat reflux for 40 min
  11. stirringthe mixture stirred at 20° C. for 2 h [until a sample
  12. customThe mixture was then evaporated
  13. distillationthe residue was distilled in a Kugelrohr (1 mm Hg, 90° C.)
  14. customto remove excess benzyl alcohol
  15. washFlash chromatography on silica gel, eluting with petroleum ether/EtOAc (3:1)

Sources & evidence

ORD record
ord-2f5a930499904b638ee6531d91e546ea
Source dataset
uspto-grants-1999_11
Patent number
US05985909

Reaction notes

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