Oxalyl chloride → (6-cyano-1-methyl-1H-indol-3-yl)glyoxylyl chloride

HRID 342059Notes

Reaction equation

HRID 342059 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=2)[CH:4]=[CH:3]1.[C:13](Cl)(=[O:17])[C:14]([Cl:16])=[O:15]>C(OCC)C>[C:11]([C:8]1[CH:9]=[C:10]2[C:5]([C:4]([C:13](=[O:17])[C:14]([Cl:16])=[O:15])=[CH:3][N:2]2[CH3:1])=[CH:6][CH:7]=1)#[N:12]

Participants

4

Reactant 2

HCID 65578Oxalyl chlorideHCID 153844931-Methyl-1H-indole-6-carbonitrile

Product 1

HCID 15384492(6-cyano-1-methyl-1H-indol-3-yl)glyoxylyl chlorideYield 96.9%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

1-methyl-1H-indole-6-carbonitrile (1.0 g, 6.4 mmole), a known compound, was dissolved in ethyl ether (Et2O) (25 mL), chilled in an ice bath and treated with oxalyl chloride (0.95 mL, 10.9 mmole, 1.7 equiv.). After removal of the ice bath, yellow solids soon precipitated. This mixture was stirred at room temperature overnight, the solids were then collected and washed with ethyl ether and dried under vacuum for 30 minutes to provide 1.53 g (96%) of (6-cyano-1-methyl-1H-indol-3-yl)oxo-acetyl chloride. This material (1.53 g, 6.2 mmole) along with 2-(1-methyl-1H-indol-3yl)-acetimidic acid isopropyl ester hydrochloride (1.66 g, 6.2 mmole, 1 equiv.) was suspended in CH2Cl2 (100 mL) and cooled in an ice bath. The mixture was treated with Et3N (3.5 mL, 24.8 mmole, 4 equiv.), stirred at 0° for 30 minutes, then at room temperature for an additional 3 hours. The reaction mixture was then diluted with CH2Cl2 (150 mL), washed with H2O (50 mL), and then 0.5N HCl (50 mL). The organic fractions were dried over MgSO4, filtered and evaporated to give a dark oil. The residue was taken up in toluene (30 mL), chilled in an ice bath, then treated with pTsOH(1.3 g, 6.8 mmole, 1.1 equiv.), then stirred at room temperature for 2 hours. The red solids which precipitated were collected, washed with a small volume of toluene, hexane, the H2O, then partitioned between 500 mL CH2Cl2 and 75 mL saturated NaHCO3. The organic layer was dried over MgSO4, filtered and evaporated to provide 2 g of a red solid. The solid was washed with cold CH2Cl2, then recrystallized from acetone/hexane to give 938 mg of 1-methyl-3-[4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-1H-indole-6-carbonitrile.

Workup

  1. temperaturechilled in an ice bath
  2. customAfter removal of the ice bath, yellow solids
  3. customsoon precipitated
  4. customthe solids were then collected
  5. washwashed with ethyl ether
  6. customdried under vacuum for 30 minutes

Sources & evidence

ORD record
ord-8671e1b8d3bd4a1e977dbeb2bfb32d92
Source dataset
uspto-grants-1999_01
Patent number
US05856517

Reaction notes

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