Triphenylphosphine → 1H-Indazole-1-carboxylic acid, 5-methyl-3-[2-(trimethylsilyl)ethynyl]-, 1,1-dimethylethyl ester

HRID 1520003Notes

Reaction equation

HRID 1520003 reaction equation
I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH3:11])[CH:9]=2)[N:4]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[N:3]=1.[CH3:19][Si:20]([C:23]#[CH:24])([CH3:22])[CH3:21].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CC([O-])=O.CC([O-])=O.[Pd+2].[Cu](I)I>[CH3:11][C:8]1[CH:9]=[C:10]2[C:5](=[CH:6][CH:7]=1)[N:4]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[N:3]=[C:2]2[C:24]#[C:23][Si:20]([CH3:22])([CH3:21])[CH3:19]

Participants

6

Reactant 3

HCID 11776TriphenylphosphineHCID 66111TrimethylsilylacetyleneHCID 20785165HCID 20785165, compound

Product 1

HCID 679810201H-Indazole-1-carboxylic acid, 5-methyl-3-[2-(trimethylsilyl)ethynyl]-, 1,1-dimethylethyl ester

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
80 °C

Procedure

In a round bottom flask were introduced tert-butyl 3-iodo-5-methyl-1H-indazole-1-carboxylate (8.3 g; 23.2 mmol; 1.0 eq.), (trimethylsilyl)acetylene (6.8 mL; 48.8 mmol; 2.1 eq.), Pd(OAc)2 (521 mg; 2.3 mmol; 0.1 eq.), triphenylphosphine (1.22 g; 4.65 mmol; 0.2 eq.) and copper iodide (442 mg; 2.32 mmol; 0.1 eq.) in TEA (57 mL). The reaction mixture was degassed and stirred at 80° C. under N2 for 1 hour. Et2O was added and the reaction mixture was filtrated through a celite pad. The filtrate was then washed twice with an aqueous saturated solution of NH4Cl and brine, dried over magnesium sulfate, filtered and concentrated. This crude was purified by flash chromatography on silica (Heptane/EtOAc, gradient from 100:0 to 10:90) to afford the title compound as a beige solid.

Workup

  1. customThe reaction mixture was degassed
  2. additionEt2O was added
  3. filtrationthe reaction mixture was filtrated through a celite pad
  4. washThe filtrate was then washed twice with an aqueous saturated solution of NH4Cl and brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThis crude was purified by flash chromatography on silica (Heptane/EtOAc, gradient from 100:0 to 10:90)

Sources & evidence

ORD record
ord-585dbd62e0b8415e8585b6d6d05c61d3
Source dataset
uspto-grants-2015_07
Patent number
US09073892B2

Reaction notes

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