Indoline → N-(5-ethoxycarbonylmethyl-4,6-dimethylindolin-7-yl)-2,2-dimethylpropanamide

HRID 1531958Notes

Reaction equation

HRID 1531958 reaction equation
C([O:3]C)#N.N1[C:13]2[C:8](=CC=CC=2)CC1.C([N:17]1[C:25]2[C:20](=[C:21]([CH3:37])[C:22]([CH2:34][C:35]#N)=[C:23]([CH3:33])[C:24]=2[NH:26][C:27](=[O:32])[C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:19][CH2:18]1)(=O)C.[OH-:38].[Na+]>C(O)CC.O>[CH2:13]([O:38][C:35]([CH2:34][C:22]1[C:21]([CH3:37])=[C:20]2[C:25](=[C:24]([NH:26][C:27](=[O:32])[C:28]([CH3:29])([CH3:30])[CH3:31])[C:23]=1[CH3:33])[NH:17][CH2:18][CH2:19]2)=[O:3])[CH3:8]

Participants

7

Reactant 4

HCID 10328Indoline2×HCID 14798Sodium HydroxideHCID 137201Cyanic acid, methyl esterHCID 15524343N-(1-acetyl-5-cyanomethyl-4,6-dimethylindolin-7-yl)-2,2-dimethylpropanamide

Product 1

HCID 12112203N-(5-ethoxycarbonylmethyl-4,6-dimethylindolin-7-yl)-2,2-dimethylpropanamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 10311-PropanolSolvent

Conditions

Temperature
90 °C

Procedure

1.27 (9H, s, —C(CH3)3), 2.26, 2.30, 2.40 (9H, s×3, —CH3×2, >NCOCH3), 3.00 (2H, br, Indoline C3—H), 3.66 (2H, s, —CH2CN), 4.05 (2H, br, Indoline C2—H), 9.21 (1H, br, >NH). (4) N-(1-Acetyl-5-cyanomethyl-4,6-dimethylindolin-7-yl)-2,2-dimethyl-propanamide (5.0 g) was suspended in n-PrOH (25 ml) and a solution of NaOH (9.6 g) in water (10 ml) was added, which was followed by stirring at 90° C. for 8 hr in an autoclave under a nitrogen atmosphere. The aqueous layer was separated, and the organic layer was neutralized with 2N-hydrochloric acid. The solvent was evaporated under reduced pressure. The residue was suspended in ETOH (200 ml), and ION HCl-EtOH (7.2 ml) was added, which was followed by refluxing for 1 hr. EtOH was evaporated under reduced pressure, and the mixture was neutralized with saturated aqueous solution of sodium hydrogencarbonate and extracted with AcOEt (200 ml). The AcOEt layer was washed with water and dried over anhydrous sodium sulfate. AcOEt was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (eluent: CHCl3/MeOH=1/0−20/1) to give 3.0 g of N-(5-ethoxycarbonylmethyl-4,6-dimethylindolin-7-yl)-2,2-dimethylpropanamide.

Workup

  1. customThe aqueous layer was separated
  2. customThe solvent was evaporated under reduced pressure
  3. additionwas added
  4. temperatureby refluxing for 1 hr
  5. customEtOH was evaporated under reduced pressure
  6. extractionextracted with AcOEt (200 ml)
  7. washThe AcOEt layer was washed with water
  8. dry with materialdried over anhydrous sodium sulfate
  9. customAcOEt was evaporated under reduced pressure
  10. customthe residue was purified by silica gel column chromatography (eluent: CHCl3/MeOH=1/0−20/1)

Sources & evidence

ORD record
ord-4e84a7b729a34f2aa523c32f1eac07ab
Source dataset
uspto-grants-2001_03
Patent number
US06200988B1

Reaction notes

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