Toluene → HCID 23125017, compound

HRID 2223364Notes

Reaction equation

HRID 2223364 reaction equation
[C:1]([O:5][C:6]([C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[C:10]([N+:17]([O-:19])=[O:18])[CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[O-].[Na+].C1(C)C=CC=CC=1.[Cl:30][C:31]1[CH:32]=[CH:33][C:34]([NH2:37])=[N:35][CH:36]=1>O1CCCC1.CO.C(Cl)(Cl)Cl.N1C=CC=CC=1>[Cl:30][C:31]1[CH:32]=[CH:33][C:34]([NH:37][C:12]([C:11]2[CH:15]=[CH:16][C:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[CH:9][C:10]=2[N+:17]([O-:19])=[O:18])=[O:14])=[N:35][CH:36]=1

Participants

9

Reactant 4

HCID 1140TolueneHCID 661742-Amino-5-chloropyridineHCID 10942334Sodium MethoxideHCID 190761834-(1,1-Dimethylethyl) 2-nitro-1,4-benzenedicarboxylate

Product 1

HCID 23125017HCID 23125017, compoundYield 56.9%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 1049PyridineSolventHCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-(t-Butoxycarbonyl)-2-nitrobenzoic acid (1.0 g) is dissolved in tetrahydrofuran (50 ml), and thereto is added 28% sodium methoxide in methanol (0.72 g). After pouring toluene, the mixture is concentrated under reduced pressure. The resulting residue is suspended in chloroform (50 ml), and thereto are added oxalyl chloride (489 μl) and N,N-dimethylformamide (2 drops) followed by stirring at room temperature for 3 hours. The reaction solution is concentrated under reduced pressure, and chloroform (20 ml) is poured to the residue to give a suspension. 5-Chloro-2-aminopyridine (480 mg) and pyridine (453 μl) are dissolved in chloroform (30 ml), and the solution is ice-cooled. To the solution is added dropwise the suspension prepared above. The reaction solution is stirred at room temperature for 8 hours and concentrated under reduced pressure. The residue is diluted with ethyl acetate, washed successively with 10% aqueous potassium hydrogen sulfate solution, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over magnesium sulfate, and evaporated to remove the solvent under reduced pressure. The resulting residue is purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=4/1) to give t-butyl 4-{[(5-chloropyridin-2-yl)amino]carbonyl}-3-nitrobenzoate (803 mg). APCI-MS M/Z: 378[M+H]+

Workup

  1. concentrationthe mixture is concentrated under reduced pressure
  2. additionare added oxalyl chloride (489 μl) and N,N-dimethylformamide (2 drops)
  3. concentrationThe reaction solution is concentrated under reduced pressure, and chloroform (20 ml)
  4. additionis poured to the residue
  5. customto give a suspension
  6. temperaturecooled
  7. additionTo the solution is added dropwise the suspension
  8. customprepared above
  9. stirringThe reaction solution is stirred at room temperature for 8 hours
  10. concentrationconcentrated under reduced pressure
  11. additionThe residue is diluted with ethyl acetate
  12. washwashed successively with 10% aqueous potassium hydrogen sulfate solution, saturated aqueous sodium hydrogen carbonate solution and saturated brine
  13. dry with materialdried over magnesium sulfate
  14. customevaporated
  15. customto remove the solvent under reduced pressure
  16. customThe resulting residue is purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=4/1)

Sources & evidence

ORD record
ord-b2241c74371d4af8a65c6f7c3e4fec20
Source dataset
uspto-grants-2008_05
Patent number
US07375119B2

Reaction notes

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