Ethyl Acetate → 4-Methoxy-7-(1,2,4-triazol-1-yl)-6-azaindol-3-yl-oxoacetic acid methyl ester

HRID 1394424Notes

Reaction equation

HRID 1394424 reaction equation
[Al+3].[Cl-].[Cl-].[Cl-].[CH3:5][O:6][C:7]1[CH:15]=[N:14][C:13]([N:16]2[CH:20]=[N:19][CH:18]=[N:17]2)=[C:12]2[C:8]=1[CH:9]=[CH:10][NH:11]2.C([O-])(=[O:23])C.[NH4+].C[CH2:27][O:28][C:29]([CH3:31])=[O:30]>C(Cl)Cl.C[N+]([O-])=O>[CH3:27][O:28][C:29](=[O:30])[C:31]([C:9]1[C:8]2[C:12](=[C:13]([N:16]3[CH:20]=[N:19][CH:18]=[N:17]3)[N:14]=[CH:15][C:7]=2[O:6][CH3:5])[NH:11][CH:10]=1)=[O:23]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 517165Ammonium AcetateHCID 6451240Aluminum(III) ChlorideHCID 207912504-Methoxy-7-(1,2,4-triazol-1-yl)-6-azaindole

Product 1

HCID 670467734-Methoxy-7-(1,2,4-triazol-1-yl)-6-azaindol-3-yl-oxoacetic acid methyl esterYield 46%

Reagents, catalysts & solvents 1

HCID 23431834Dichloromethane nitromethaneSolvent

Procedure

To a mixture of AlCl3 (0.665 g, 5.0 mmol) in 4 mL of CH2Cl2—MeNO2 (4:1) was added 4-methoxy-7-(1,2,4-triazol-1-yl)-6-azaindole (0.108 g, 0.50 mmol) as a solid. To the resulting solution was added methyl oxalyl chloride (0.185 mL, 2.0 mmol) dropwise and then the mixture was stirred at room temperature for 16 h. The reaction mixture was then carefully poured into 20% aqueous ammonium acetate and EtOAc was added. The resulting emulsion was filtered and the residue was washed with additional EtOAc. The organic phase was washed (brine), dried (Na2SO4) and evaporated, and the residue was triturated with MeOH to give 4-methoxy-7-(1,2,4-triazol-1-yl)-6-azaindol-3-yl-oxoacetic acid methyl ester (0.069 g, 46%) as a yellow solid: MS m/e 300 (M−H)−. This material (0.069 g, 0.229 mmol) was taken up in 3 mL of MeOH, 1M K2CO3 (0.9 mL, 0.9 mmol) was added and the mixture was stirred at room temperature for 20 h. The solution was then diluted with an equal volume of water and concentrated in vacuo. The resulting aqueous solution was cooled at 0° C. and acidified to pH 1-2 with 6N HCl. This gave a bright yellow precipitate which was filtered, washed with cold 0.1N HCl and then with ether. The wet solid was suspended in ether with sonication and then it was filtered and dried in vacuo to give the title compound (0.049 g, 75%) as a yellow powder:

Workup

  1. additionwas added
  2. filtrationThe resulting emulsion was filtered
  3. washthe residue was washed with additional EtOAc
  4. washThe organic phase was washed (brine)
  5. dry with materialdried (Na2SO4)
  6. customevaporated
  7. customthe residue was triturated with MeOH

Sources & evidence

ORD record
ord-8a961f2982be4ce0a10c7f21ab39feb9
Source dataset
uspto-grants-2008_03
Patent number
US07348337B2

Reaction notes

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