Potassium Phosphate, Tribasic → 5-cyclopropyl-1-(2-trimethylsilanylethoxymethyl)-1H-indazole

HRID 246196ノート

反応式

HRID 246196 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[N:6]=[CH:5]2.[CH:19]1(B(O)O)[CH2:21][CH2:20]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CCOC(C)=O.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH:19]1([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[N:7]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[N:6]=[CH:5]3)[CH2:21][CH2:20]1

参加物

9

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 58259768HCID 58259768、化合物

生成物 1

HCID 712800795-cyclopropyl-1-(2-trimethylsilanylethoxymethyl)-1H-indazole収率 77.1%

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒2 回HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
100 °C

実験手順

A 250 ml 2-neck round-bottomed flask was charged with 5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (2.5 g, 7.64 mmol), cyclopropylboronic acid (1.18 g, 13.7 mmol), palladium (II) acetate (85.7 mg, 0.38 mmol), tricyclohexylphosphine (214 mg, 0.764 mmol), potassium phosphate tribasic (3.24 g, 15.3 mmol), toluene (40 ml) and water (4 ml). The reaction mixture was stirred at 100° C. overnight. The reaction mixture was cooled to room temperature and then diluted with EtOAc (100 ml) and water (20 ml). The mixture was extracted with EtOAc (100 mL). The organic layers were washed with water (20 mL) and brine (20 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated. The residue was absorbed onto SiO2 and purified by chromatography over SiO2 with EtOAc/CH2Cl2 (gradient: 0-10% EtOAc) to afford 1.7 g (77%) of 5-cyclopropyl-1-(2-trimethylsilanylethoxymethyl)-1H-indazole as a light yellow oil. 1H NMR (300 MHz, CDCl3) δ: 7.93 (s, 1H), 7.48 (d, J=8.7 Hz, 1H), 7.44 (s, 1H), 7.19 (dd, J=8.5, 1.7 Hz, 1H), 3.53 (app t, J=8.3 Hz, 2H), 1.93-2.12 (m, 1H), 0.92-1.04 (m, 2H), 0.88 (app t, J=8.3 Hz, 2H), 0.64-0.78 (m, 2H), −0.07 (s, 9H).

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionThe mixture was extracted with EtOAc (100 mL)
  3. washThe organic layers were washed with water (20 mL) and brine (20 mL)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was absorbed onto SiO2
  8. custompurified by chromatography over SiO2 with EtOAc/CH2Cl2 (gradient: 0-10% EtOAc)

出典と根拠

ORDレコード
ord-27b83e5a94414219918dfd1b19ba6a70
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

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