Water → (5-chloro-3-cyano-2-oxo-2,3-dihydro-1H-indol-3-yl)-cyanoacetic acid methyl ester

HRID 883642Notes

Reaction equation

HRID 883642 reaction equation
[CH3:1][O:2][C:3](=[O:18])[C:4](=[C:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([Cl:16])[CH:14]=2)[NH:9][C:8]1=[O:17])[C:5]#[N:6].[C-:19]#[N:20].[K+].O>CO>[CH3:1][O:2][C:3](=[O:18])[CH:4]([C:7]1([C:19]#[N:20])[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([Cl:16])[CH:14]=2)[NH:9][C:8]1=[O:17])[C:5]#[N:6]

Participants

5

Reactant 3

HCID 962WaterHCID 9032Potassium CyanideHCID 67426106(5-Chloro-2-oxo-1,2-dihydro-indol-3-ylidene)-cyanoacetic acid methyl ester

Product 1

HCID 24829234(5-chloro-3-cyano-2-oxo-2,3-dihydro-1H-indol-3-yl)-cyanoacetic acid methyl esterYield 86%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A stirred suspension of crude (5-chloro-2-oxo-1,2-dihydro-indol-3-ylidene)-cyanoacetic acid methyl ester, intermediate 1 (56.0 g, 0.21 mol) in methanol (750 ml) was treated, in portions, with potassium cyanide (13.8 g, 0.21 mol) followed by water (45 ml). The mixture was stirred at ambient temperature for 7 hours and the resultant black solution was left to stand overnight. The solvent was removed in vacuo, water (500 ml) was added and the mixture acidified by the addition of 2M hydrochloric acid [CAUTION: TRACES OF CYANIDE MAY STILL BE PRESENT!]. The mixture was extracted with dichloromethane (3×300 ml). The combined extracts were washed with water (2×300 ml) and dried (MgSO4). The solvent was removed in vacuo to give the crude (5-chloro-3-cyano-2-oxo-2,3-dihydro-1H-indol-3-yl)-cyanoacetic acid methyl ester as a pale-brown solid (53.3 g, 86%). This was a mixture of diastereomers, which was sufficiently pure by 1H NMR for subsequent reaction.

Workup

  1. waitthe resultant black solution was left
  2. waitto stand overnight
  3. customThe solvent was removed in vacuo, water (500 ml)
  4. additionwas added
  5. additionthe mixture acidified by the addition of 2M hydrochloric acid [CAUTION: TRACES OF CYANIDE MAY STILL BE PRESENT!]
  6. extractionThe mixture was extracted with dichloromethane (3×300 ml)
  7. washThe combined extracts were washed with water (2×300 ml)
  8. dry with materialdried (MgSO4)
  9. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-66948cb0bfe04f289f2d4a8e63bf42a5
Source dataset
uspto-grants-2012_08
Patent number
US08236963B2

Reaction notes

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