Methane → Alpha-acetamido-6-chloro-3-indoleacrylic acid

HRID 1447314Notes

Reaction equation

HRID 1447314 reaction equation
C[O:2][C:3](=[O:20])[C:4]([NH:16][C:17](=[O:19])[CH3:18])=[CH:5][C:6]1[C:14]2[C:9](=[CH:10][C:11]([Cl:15])=[CH:12][CH:13]=2)[NH:8][CH:7]=1.[OH-].[Na+].Cl.C>O.CO>[C:17]([NH:16][C:4](=[CH:5][C:6]1[C:14]2[C:9](=[CH:10][C:11]([Cl:15])=[CH:12][CH:13]=2)[NH:8][CH:7]=1)[C:3]([OH:20])=[O:2])(=[O:19])[CH3:18]

Participants

7

Reactant 4

HCID 297MethaneHCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 54310075alpha-Acetamido-6-chloro-3-indoleacrylic acid methylester

Product 1

HCID 54300941Alpha-acetamido-6-chloro-3-indoleacrylic acidYield 91%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

A 2-l. three-necked flask, equipped with thermometer mechanical stirrer and reflux condenser was charged with 90.4 g (0.31 moles) of alpha-acetamido-6-chloro-3-indoleacrylic acid methylester, 200 ml (0.40 moles) of 2 N aqueous sodium hydroxide and 400 ml of methylalcohol. The mixture was stirred and heated at an internal temperature of 55°-58° for 90 minutes. 800 ml of distilled water was added and the brown slightly turbid solution filtered through a Buchner funnel. The clear filtrate was acidified with 90 ml (0.54 moles) of 6 N aqueous hydrochloric acid. The precipitate was collected on a Buchner funnel and washed with distilled water. The wet cake was transferred into flask and suspended in 180 ml of dimethylformamide and 600 ml of methyl alcohol. The mixture was heated on a steam bath to reflux until a brown, slightly turbid solution was formed. 6 g of charcoal was added and reflux was continued for 10 minutes. The hot mixture was quickly filtered through a bed of Celite. The deep yellow, clear filtrate was transferred into a 2-l. flask, equipped with reflux-condenser and dropping funnel and brought again to reflux under an atmosphere of nitrogen. 240 ml of distilled water was added over a 5 minute period while reflux was maintained. The mixture was allowed to stand overnight under an atmosphere of nitrogen at room temperature. The product was collected by suction filtration, washed with methylalcohol-water 1:1 and dried at 85°/0.5 mmHg, to constant weight to give 78.6 g (86%) of product, as yellow crystals, m.p. 225°.

Workup

  1. customthree-necked flask, equipped with thermometer mechanical stirrer
  2. temperaturereflux condenser
  3. temperatureheated at an internal temperature of 55°-58° for 90 minutes
  4. filtrationthe brown slightly turbid solution filtered through a Buchner funnel
  5. customThe precipitate was collected on a Buchner funnel
  6. washwashed with distilled water
  7. customThe wet cake was transferred into flask
  8. temperatureThe mixture was heated on a steam bath
  9. temperatureto reflux until a brown, slightly turbid solution
  10. customwas formed
  11. temperaturereflux
  12. filtrationThe hot mixture was quickly filtered through a bed of Celite
  13. customflask, equipped with reflux-condenser
  14. temperatureto reflux under an atmosphere of nitrogen
  15. addition240 ml of distilled water was added over a 5 minute period
  16. temperaturewhile reflux
  17. temperaturewas maintained
  18. waitto stand overnight under an atmosphere of nitrogen at room temperature
  19. filtrationThe product was collected by suction filtration
  20. washwashed with methylalcohol-water 1:1
  21. customdried at 85°/0.5 mmHg

Sources & evidence

ORD record
ord-1b9c9a309bd74deaa29d1031e7aea5a4
Source dataset
uspto-grants-1982_02
Patent number
US04316847

Reaction notes

Loading…