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

Participants

Role	Name	HCID	Charge
Reactant	Indole	HCID 798	—
Reactant	Cesium carbonate	HCID 10796	—
Reactant	1,4-Dioxane	HCID 31275	—
Reactant	Methylboronic Acid	HCID 139377	—
Catalyst	Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)	HCID 178418228	—
Solvent	Water	HCID 962	—
Product	4,6-dimethyl-1H-indole-3-carboxylic acid	HCID 82404736	40.9%

Reaction Conditions

Temperature	110 °C

Reaction Steps

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.

Provenance & Evidence

DOI	10.6084/m9.figshare.5104873.v1
Patent number	US09434724B2
Source dataset	uspto-grants-2016_09
ORD ID	ord-863bbacc59ae4f1498b0036fe5995fc5
Source note	uspto-grants-2016_09