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

HRID 246196노트

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HRID 246196 반응식
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

참가 물질

9

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 58259768HCID 58259768, 화합물

생성물 1

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

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 962Water용매2회HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

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온도
100 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-27b83e5a94414219918dfd1b19ba6a70
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658646B2

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