Indole → 4,6-dimethyl-1H-indole-3-carboxylic acid

HRID 57318

Reaction equation

HRID 57318 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=C[CH:8]=2)[CH:3]=[CH:2]1.[CH3:10]B(O)O.[C:14]([O-:17])([O-])=[O:15].[Cs+].[Cs+].O1[CH2:25][CH2:24]OCC1>O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:10][C:5]1[CH:6]=[C:24]([CH3:25])[CH:8]=[C:9]2[C:4]=1[C:3]([C:14]([OH:17])=[O:15])=[CH:2][NH:1]2

Participants

7

Reactant 4

HCID 798IndoleHCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 139377Methylboronic Acid

Product 1

HCID 824047364,6-dimethyl-1H-indole-3-carboxylic acidYield 40.9%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×

Conditions

Temperature
110 °C

Procedure

A mixture of indole 5 (690 mg, 3.28 mmol), methylboronic acid (495 mg, 3.94 mmol, 1.2 eq.), Pd(dppf)Cl2 (180 mg, 0.656 mmol, 0.2 eq.) and Cs2CO3 (3.20 g, 9.84 mmol, 3.0 eq.) in dioxane (21 mL) and water (3 mL) was stirred at 110° C. overnight under N2. The mixture was diluted with water and extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography (petroleum ether/EtOAc=5/1) to give the desired product (170 mg, 1.17 mmol, 40.9%) as a white solid.

Workup

  1. extractionextracted with EtOAc
  2. washThe combined extracts were washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography (petroleum ether/EtOAc=5/1)

Sources & evidence

ORD record
ord-863bbacc59ae4f1498b0036fe5995fc5
Source dataset
uspto-grants-2016_09
Patent number
US09434724B2

Linked notes

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