Indole-3-acetamide → Arcyriarubin A

HRID 368740

Reaction equation

HRID 368740 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][C:11]([NH2:13])=[O:12])=[CH:2]1.C[O:15][C:16]([C:18]([C:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[NH:22][CH:21]=1)=O)=O.CC(C)([O-])C.[K+].CCOC(C)=O>C1COCC1.[Cl-].[Na+].O.O>[CH:6]1[CH:5]=[C:4]2[C:3]([C:10]3[C:11](=[O:12])[NH:13][C:16](=[O:15])[C:18]=3[C:20]3[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[NH:22][CH:21]=3)=[CH:2][NH:1][C:9]2=[CH:8][CH:7]=1

Participants

8

Reactant 4

HCID 397Indole-3-acetamideHCID 8857Ethyl AcetateHCID 588944Methyl 3-indoleglyoxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 2399Arcyriarubin AYield 108.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

A suspension of indole-3-acetamide (1.00 g, 5.74 mmol) and methyl indolyl-3-glyoxylate (1.28 g, 6.30 mmole) in THF (10 mL) was treated with a 1 molar solution of potassium tert-butoxide in THF (17.2 mL, 17.2 mmol) at room temperature under N2. The resultant dark reaction mixture was stirred 3 hrs. at room temperature and was then treated with concentrated (37%) HCl (8 mL) allowing the reaction to exotherm. The reaction was worked up extractively using EtOAc (125 mL), water (2×100 mL), brine (25 ml) and the organic layer dried (MgSO4) and solvent removed in vacuo to give a solid that was purified by flash chromatography using a gradient of 2:1 to 1:1 hexanes:EtOAc to give 2.04 g (100%) of arcyriarubin A [1.28 g (68%) when using glyoxylyl chloride]. 3,4-(3-indolyl-1H-pyrrole-2,5-dione could also be recrystallized from EtOH to give a stiochiometric ethanol monosolvate in high purity (>99%) and yield (88%). NMR. MS (FD) m/z=327 (M+, 100%). Analytical calculated for C22H19N3O3C, 70.76; H, 5.13; N, 11.25. Found C, 70.97; H, 5.22; N, 11.12.

Workup

  1. customThe resultant dark reaction mixture
  2. additionat room temperature and was then treated
  3. concentrationwith concentrated (37%) HCl (8 mL)
  4. customthe reaction
  5. dry with materialthe organic layer dried (MgSO4) and solvent
  6. customremoved in vacuo
  7. customto give a solid
  8. customthat was purified by flash chromatography

Sources & evidence

ORD record
ord-c8ef56f06b214ae688587a1d6ba59984
Source dataset
uspto-grants-2000_10
Patent number
US06133452

Linked notes

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