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

HRID 250255ノート

反応式

HRID 250255 の反応式
[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]

参加物

9

反応物 4

HCID 313Hydrochloric AcidHCID 62657Potassium Phosphate, TribasicHCID 574432723-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 672714736-Chloro-1-isopropyl-2-methyl-1H-indole-3-carboxylic acid methyl ester

生成物 1

HCID 672718996-(4-Hydroxy-2-methyl-phenyl)-1-isopropyl-2-methyl-1H-indole-3-carboxylic acid methyl ester収率 88.1%

試薬・触媒・溶媒 4

HCID 75806Tricyclohexylphosphine触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

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).

後処理

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

出典と根拠

ORDレコード
ord-1b982d3c3d99461c8e50912a92b917fa
出典データセット
uspto-grants-2011_01
特許番号
US07863302B2

反応ノート

読み込み中…