Hydrochloric Acid → 6-(4-Hydroxy-2-methyl-phenyl)-1-isopropyl-2-methyl-1H-indole-3-carboxylic acid methyl ester

HRID 250255Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10](Cl)=[CH:11][CH:12]=2)[N:7]([CH:15]([CH3:17])[CH3:16])[C:6]=1[CH3:18])=[O:4].[CH3:19][C:20]1[CH:21]=[C:22]([OH:35])[CH:23]=[CH:24][C:25]=1B1OC(C)(C)C(C)(C)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].Cl>O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.O1CCOCC1>[CH3:1][O:2][C:3]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([C:25]3[CH:24]=[CH:23][C:22]([OH:35])=[CH:21][C:20]=3[CH3:19])=[CH:11][CH:12]=2)[N:7]([CH:15]([CH3:17])[CH3:16])[C:6]=1[CH3:18])=[O:4]

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 6-chloro-1-isopropyl-2-methyl-1H-indole-3-carboxylic acid methyl ester (200 mg, 0.75 mmol), 3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenol (351 mg, 1.50 mmol), dioxane (2.5 mL), potassium phosphate tribasic, N-hydrate (2.59 g, 1.28 mmol), tris(dibenzylideneacetone)dipalladium(0) (12 mg, 0.013 mmol) and tricyclohexylphosphine (9 mg, 0.03 mmol) is stirred under nitrogen at 120° C. for 16 h. The mixture is acidified with 1N HCl, diluted with water, and extracted with ether. The combined ether layers are washed with brine and dried over MgSO4. The crude product is purified via flash chromatography (40 g SiO2) cluting with 30% THF-heptane to yield the title compound (223 mg, 88%) as a white solid. ES/MS ma/c 338.0 (M+1).

Workup

extractionextracted with ether
washThe combined ether layers are washed with brine
dry with materialdried over MgSO4
customThe crude product is purified via flash chromatography (40 g SiO2)

Sources & evidence

ORD record: ord-1b982d3c3d99461c8e50912a92b917fa
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07863302B2

Reaction notes

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