Hydrochloric Acid → Alpha-acetamido-6-methylindole-3-acrylic acid monohydrate

HRID 127505Notes

Reaction equation

HRID 127505 reaction equation
C([O:3][C:4](=[O:21])[C:5]([NH:17][C:18](=[O:20])[CH3:19])=[CH:6][C:7]1[C:15]2[C:10](=[CH:11][C:12]([CH3:16])=[CH:13][CH:14]=2)[NH:9][CH:8]=1)C.CO.[OH-].[Na+].Cl>O>[OH2:3].[C:18]([NH:17][C:5](=[CH:6][C:7]1[C:15]2[C:10](=[CH:11][C:12]([CH3:16])=[CH:13][CH:14]=2)[NH:9][CH:8]=1)[C:4]([OH:21])=[O:3])(=[O:20])[CH3:19]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 54175825Alpha-acetamido-6-methylindole-3-acrylic acid ethylester

Product 1

HCID 70549486Alpha-acetamido-6-methylindole-3-acrylic acid monohydrate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

three-necked flask, equipped with a mechanical stirrer, a thermometer and a dropping funnel was charged with 159.5 g (0.56 mol) of crude alpha-acetamido-6-methylindole-3-acrylic acid ethylester and 475 ml of methanol. The mixture was heated in an oil bath to 50°. A solution of 66.8 g (1.67 mol) of sodium hydroxide in 320 ml of water was added over 3 minutes and the resulting brown solution was stirred at 50° for 45 minutes. The reaction mixture was cooled with an ice bath to 25° and 600 ml of 4 N hydrochloric acid was added over 20 minutes at 25°. The precipitate was collected on a Buchner funnel, washed with 900 ml of water and dried at 50° overnight and at 60°/0.5 mm for 3 hours. The beige solid (146 g) was dissolved in 1 l of methanol and 175 ml of dimethylformamide at reflux. 10 g of charcoal was added and reflux was continued for 10 minutes. The mixture was filtered through a bed of Celite and the clear brown solution was brought again to reflux. 425 ml of water was added over a 20 minute period, while reflux was maintained. The mixture was refrigerated for 3 hours. The product was collected by suction filtration, washed with 750 ml of 1:1 methanol--water and dried at 50° for 24 hours (const. weight) to yield 119.9 g (69%, based on 6-methylindole-3-carboxaldehyde of product as yellow crystals, m.p. 229° (dec.).

Workup

  1. customthree-necked flask, equipped with a mechanical stirrer
  2. temperatureThe mixture was heated in an oil bath to 50°
  3. temperatureThe reaction mixture was cooled with an ice bath to 25°
  4. customThe precipitate was collected on a Buchner funnel
  5. washwashed with 900 ml of water
  6. customdried at 50° overnight and at 60°/0.5 mm for 3 hours
  7. dissolutionThe beige solid (146 g) was dissolved in 1 l of methanol
  8. temperature175 ml of dimethylformamide at reflux
  9. addition10 g of charcoal was added
  10. temperaturereflux
  11. waitwas continued for 10 minutes
  12. filtrationThe mixture was filtered through a bed of Celite
  13. temperatureto reflux
  14. addition425 ml of water was added over a 20 minute period
  15. temperaturewhile reflux
  16. temperaturewas maintained
  17. waitThe mixture was refrigerated for 3 hours
  18. filtrationThe product was collected by suction filtration
  19. washwashed with 750 ml of 1:1 methanol
  20. dry with materialwater and dried at 50° for 24 hours (const. weight)
  21. customto yield 119.9 g (69%

Sources & evidence

ORD record
ord-27b931bf163b454f9941d1b2d49dd76f
Source dataset
uspto-grants-1981_03
Patent number
US04256641

Reaction notes

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