Hydrochloric Acid → 1-Acetyl-3-(2-acetoxyethyl)-5-bromo-4,6-dimethyl-7-nitroindoline

HRID 1531964Notes

Reaction equation

HRID 1531964 reaction equation
C(OC)#N.N1C2C(=CC=CC=2)CC1.[C:14]([N:17]1[C:25]2[C:20](=[C:21]([CH3:27])[CH:22]=[C:23]([CH3:26])[CH:24]=2)[CH:19]([CH2:28][CH2:29][O:30][C:31](=[O:33])[CH3:32])[CH2:18]1)(=[O:16])[CH3:15].[Br:34]Br.[N+:36]([O-:39])(O)=[O:37].Cl>CC(O)=O>[C:14]([N:17]1[C:25]2[C:20](=[C:21]([CH3:27])[C:22]([Br:34])=[C:23]([CH3:26])[C:24]=2[N+:36]([O-:39])=[O:37])[CH:19]([CH2:28][CH2:29][O:30][C:31](=[O:33])[CH3:32])[CH2:18]1)(=[O:16])[CH3:15]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 944Nitric AcidHCID 10328Indoline4×HCID 24408BromineHCID 137201Cyanic acid, methyl esterHCID 222473471-Acetyl-3-(2-acetoxyethyl)-4,6-dimethylindoline

Product 1

HCID 222473151-Acetyl-3-(2-acetoxyethyl)-5-bromo-4,6-dimethyl-7-nitroindoline

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Procedure

1.60·2.20 (2H, m, —CH2 CH2O—), 2.04 (3H, s, -OCH3), 2.24 (3H, s, >NCOCH3), 2.24, 2.30 (6H, sx 2, —CH3×2), 3.34 (1H, m, Indoline C3—H), 3.94 (2H, m, Indoline C2—H), 4.12 (2H, t, J=7.1 Hz, —CH2 CH2O—), 6.67 (1H, s, Indoline C5—H), 7.90 (1H, s, Indoline C7—H). (3) 1-Acetyl-3-(2-acetoxyethyl)-4,6-dimethylindoline (2.0 g) was dissolved in AcOH (40 ml) and Br2 (1.9 g) was added, which was followed by stirring at room temperature for 30 min. The reaction mixture was poured into ice water and precipitate was collected by filtration. The precipitate was dissolved in CHCl3, and the mixture was washed with water and dried over anhydrous sodium sulfate. CHCl3 was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: CHCl3/MeOH=50/1−10/1) to give 2.7 g of crude crystals of 1-acetyl-3-(2-acetoxyethyl)-5-bromo-4,6-dimethylindoline. The crude crystals were added by portions to a mixture of nitric acid (0.47 ml), AcOH (10 ml) and conc. hydrochloric acid (10 ml) under ice-cooling, and the mixture was stirred at the same temperature for 4 hr. The reaction mixture was poured into ice water and precipitate was collected by filtration. The precipitate was dissolved in CHCl3. After washing with water, the mixture was dried over anhydrous sodium sulfate and CHCl3 was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: CHCl3/MeOH=50/1−10/1) to give 1.4 g of 1-acetyl-3-(2-acetoxyethyl)-5-bromo-4,6-dimethyl-7-nitroindoline.

Workup

  1. filtrationwas collected by filtration
  2. dissolutionThe precipitate was dissolved in CHCl3
  3. washthe mixture was washed with water
  4. dry with materialdried over anhydrous sodium sulfate
  5. customCHCl3 was evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (eluent: CHCl3/MeOH=50/1−10/1)
  7. customto give 2.7 g of crude crystals of 1-acetyl-3-(2-acetoxyethyl)-5-bromo-4,6-dimethylindoline
  8. temperaturecooling
  9. stirringthe mixture was stirred at the same temperature for 4 hr
  10. filtrationwas collected by filtration
  11. dissolutionThe precipitate was dissolved in CHCl3
  12. washAfter washing with water
  13. dry with materialthe mixture was dried over anhydrous sodium sulfate and CHCl3
  14. customwas evaporated under reduced pressure
  15. customThe residue was purified by silica gel column chromatography (eluent: CHCl3/MeOH=50/1−10/1)

Sources & evidence

ORD record
ord-702f232fe082466e8a6e3b1170e87556
Source dataset
uspto-grants-2001_03
Patent number
US06200988B1

Reaction notes

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