Methyl cyanoacetate → methyl (2Z)-(5-chloro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)(cyano)acetate

HRID 883638Notes

Reaction equation

HRID 883638 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=O.[C:13]([CH2:15][C:16]([O:18][CH3:19])=[O:17])#[N:14].N1CCCCC1>CO>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])/[C:5]/2=[C:15](/[C:13]#[N:14])\[C:16]([O:18][CH3:19])=[O:17]

Participants

5

Reactant 3

HCID 7747Methyl cyanoacetateHCID 8082PiperidineHCID 872035-chloro-1H-indole-2,3-dione

Product 1

HCID 24828581methyl (2Z)-(5-chloro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)(cyano)acetateYield 90%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A stirred mixture of 5-chloro-1H-indole-2,3-dione, starting material VIII, (90.8 g, 0.5 mol) and methyl cyanoacetate (44.1 ml, 0.5 mol) in methanol (1000 ml) was treated with piperidine (2 ml) and heated under reflux for 5 hours before standing overnight at ambient temperature. The crude (5-chloro-2-oxo-1,2-dihydro-indol-3-ylidene)-cyanoacetic acid methyl ester was removed by filtration, washed with cold methanol (2×150 ml) and dried in vacuo to give 117.6 g (90%) of a dark purple solid. This was a 6.5:1 mixture of geometric isomers which was sufficiently pure by 1H NMR for subsequent reaction.

Workup

  1. temperatureheated
  2. temperatureunder reflux for 5 hours
  3. customThe crude (5-chloro-2-oxo-1,2-dihydro-indol-3-ylidene)-cyanoacetic acid methyl ester was removed by filtration
  4. washwashed with cold methanol (2×150 ml)
  5. customdried in vacuo

Sources & evidence

ORD record
ord-052d514d95bf484c975e7cc3bfb8ee7e
Source dataset
uspto-grants-2012_08
Patent number
US08236963B2

Reaction notes

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