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

HRID 246196Notes

Reaction equation

HRID 246196 reaction equation
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

Participants

9

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-27b83e5a94414219918dfd1b19ba6a70
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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